@article {2020|2117, title = {Aggregation of disease-related peptides.}, journal = {Prog Mol Biol Transl Sci}, volume = {170}, year = {2020}, month = {2020}, pages = {435-460}, abstract = {

Protein misfolding and aggregation of amyloid proteins is the fundamental cause of more than 20 diseases. Molecular mechanisms of the self-assembly and the formation of the toxic aggregates are still elusive. Computer simulations have been intensively used to study the aggregation of amyloid peptides of various amino acid lengths related to neurodegenerative diseases. We review atomistic and coarse-grained simulations of short amyloid peptides aimed at determining their transient oligomeric structures and the early and late aggregation steps.

}, issn = {1878-0814}, doi = {10.1016/bs.pmbts.2019.12.002}, author = {Phuong Hoang Nguyen and Sterpone, Fabio and Philippe Derreumaux} } @article {2019|2109, title = {Amyloid-β (29{\textendash}42) Dimeric Conformations in Membranes Rich in Omega-3 and Omega-6 Polyunsaturated Fatty Acids}, journal = {The Journal of Physical Chemistry B}, volume = {123}, year = {2019}, pages = {2687{\textendash}2696}, author = {Lu, Yan and Shi, Xiao-Feng and Phuong Hoang Nguyen and Sterpone, Fabio and Salsbury Jr, Freddie R and Philippe Derreumaux} } @article {2019|2122, title = {Modelling lipid systems in fluid with Lattice Boltzmann Molecular Dynamics simulations and hydrodynamics}, journal = {Scientific Reports}, volume = {9}, year = {2019}, pages = {16450}, abstract = {

In this work we present the coupling between Dry Martini, an efficient implicit solvent coarse-grained model for lipids, and the Lattice Boltzmann Molecular Dynamics (LBMD) simulation technique in order to include naturally hydrodynamic interactions in implicit solvent simulations of lipid systems. After validating the implementation of the model, we explored several systems where the action of a perturbing fluid plays an important role. Namely, we investigated the role of an external shear flow on the dynamics of a vesicle, the dynamics of substrate release under shear, and inquired the dynamics of proteins and substrates confined inside the core of a vesicle. Our methodology enables future exploration of a large variety of biological entities and processes involving lipid systems at the mesoscopic scale where hydrodynamics plays an essential role, e.g. by modulating the migration of proteins in the proximity of membranes, the dynamics of vesicle-based drug delivery systems, or, more generally, the behaviour of proteins in cellular compartments.

}, isbn = {2045-2322}, doi = {10.1038/s41598-019-52760-y}, url = {https://doi.org/10.1038/s41598-019-52760-y}, author = {F. Brandner, Astrid and Timr, Stepan and Melchionna, Simone and Philippe Derreumaux and Marc Baaden and Sterpone, Fabio} } @article {2019|2120, title = {Multiscale Aggregation of the Amyloid Aβ16{\textendash}22 Peptide: From Disordered Coagulation and Lateral Branching to Amorphous Prefibrils}, journal = {The Journal of Physical Chemistry Letters}, volume = {10}, year = {2019}, pages = {1594-1599}, doi = {10.1021/acs.jpclett.9b00423}, url = {https://doi.org/10.1021/acs.jpclett.9b00423}, author = {Chiricotto, Mara and Melchionna, Simone and Philippe Derreumaux and Sterpone, Fabio} } @article {2019|2121, title = {OPEP6: A New Constant-pH Molecular Dynamics Simulation Scheme with OPEP Coarse-Grained Force Field}, journal = {Journal of Chemical Theory and Computation}, volume = {15}, year = {2019}, pages = {3875-3888}, doi = {10.1021/acs.jctc.9b00202}, url = {https://doi.org/10.1021/acs.jctc.9b00202}, author = {Barroso da Silva, Fernando Luis and Sterpone, Fabio and Philippe Derreumaux} } @article {2019|2119, title = {Stability Effect of Quinary Interactions Reversed by Single Point Mutations}, journal = {Journal of the American Chemical Society}, volume = {141}, year = {2019}, pages = {4660-4669}, doi = {10.1021/jacs.8b13025}, url = {https://doi.org/10.1021/jacs.8b13025}, author = {Gnutt, David and Timr, Stepan and Ahlers, Jonas and K{\"o}nig, Benedikt and Manderfeld, Emily and Heyden, Matthias and Sterpone, Fabio and Ebbinghaus, Simon} } @article {2018|2035, title = {Molecular Mechanism of Protein Unfolding under Shear: A Lattice Boltzmann Molecular Dynamics Study.}, journal = {J Phys Chem B}, volume = {122}, year = {2018}, month = {2018 Feb 08}, pages = {1573-1579}, abstract = {

Proteins are marginally stable soft-matter entities that can be disrupted using a variety of perturbative stresses, including thermal, chemical, or mechanical ones. Fluid under extreme flow conditions is a possible route to probe the weakness of biomolecules and collect information on the molecular cohesive interactions that secure their stability. Moreover, in many cases, physiological flow triggers the functional response of specialized proteins as occurring in blood coagulation or cell adhesion. We deploy the Lattice Boltzmann molecular dynamics technique based on the coarse-grained model for protein OPEP to study the mechanism of protein unfolding under Couette flow. Our simulations provide a clear view of how structural elements of the proteins are affected by shear, and for the simple study case, the β-hairpin, we exploited the analogy to pulling experiments to quantify the mechanical forces acting on the protein under shear.

}, issn = {1520-5207}, doi = {10.1021/acs.jpcb.7b10796}, author = {Sterpone, Fabio and Philippe Derreumaux and Melchionna, Simone} } @article {2018|2129, title = {Probing the quality control mechanism of the twin-arginine translocase with folding variants of a -designed heme protein.}, journal = {J Biol Chem}, volume = {293}, year = {2018}, month = {2018 05 04}, pages = {6672-6681}, abstract = {

Protein transport across the cytoplasmic membrane of bacterial cells is mediated by either the general secretion (Sec) system or the twin-arginine translocase (Tat). The Tat machinery exports folded and cofactor-containing proteins from the cytoplasm to the periplasm by using the transmembrane proton motive force as a source of energy. The Tat apparatus apparently senses the folded state of its protein substrates, a quality-control mechanism that prevents premature export of nascent unfolded or misfolded polypeptides, but its mechanistic basis has not yet been determined. Here, we investigated the innate ability of the model Tat system to recognize and translocate -designed protein substrates with experimentally determined differences in the extent of folding. Water-soluble, four-helix bundle maquette proteins were engineered to bind two, one, or no heme cofactors, resulting in a concomitant reduction in the extent of their folding, assessed with temperature-dependent CD spectroscopy and one-dimensional H NMR spectroscopy. Fusion of the archetypal N-terminal Tat signal peptide of the trimethylamine--oxide (TMAO) reductase (TorA) to the N terminus of the protein maquettes was sufficient for the Tat system to recognize them as substrates. The clear correlation between the level of Tat-dependent export and the degree of heme -induced folding of the maquette protein suggested that the membrane-bound Tat machinery can sense the extent of folding and conformational flexibility of its substrates. We propose that these artificial proteins are ideal substrates for future investigations of the Tat system\&$\#$39;s quality-control mechanism.

}, keywords = {Amino Acid Sequence, Bacterial Proteins, Circular Dichroism, Escherichia coli, Escherichia coli Proteins, Heme-Binding Proteins, Hemeproteins, Membrane Transport Proteins, Methylamines, Models, Molecular, Oxidoreductases, N-Demethylating, Periplasm, Protein Folding, Protein Sorting Signals, Protein Stability, Protein Transport, Proton Magnetic Resonance Spectroscopy, Substrate Specificity, Temperature}, issn = {1083-351X}, doi = {10.1074/jbc.RA117.000880}, author = {Sutherland, George A and Grayson, Katie J and Adams, Nathan B P and Mermans, Daphne M J and Jones, Alexander S and Robertson, Angus J and Auman, Dirk B and Brindley, Amanda A and Sterpone, Fabio and Tuffery, Pierre and Philippe Derreumaux and Dutton, P Leslie and Robinson, Colin and Hitchcock, Andrew and Hunter, C Neil} } @article {2018|2138, title = {Three Weaknesses for Three Perturbations: Comparing Protein Unfolding Under Shear, Force, and Thermal Stresses}, journal = {J Phys Chem B}, volume = {122}, year = {2018}, month = {Dec}, pages = {11922-11930}, abstract = {

The perturbation of a protein conformation by a physiological fluid flow is crucial in various biological processes including blood clotting and bacterial adhesion to human tissues. Investigating such mechanisms by computer simulations is thus of great interest, but it requires development of ad hoc strategies to mimic the complex hydrodynamic interactions acting on the protein from the surrounding flow. In this study, we apply the Lattice Boltzmann Molecular Dynamics (LBMD) technique built on the implicit solvent coarse-grained model for protein Optimized Potential for Efficient peptide structure Prediction (OPEP) and a mesoscopic representation of the fluid solvent, to simulate the unfolding of a small globular cold-shock protein in shear flow and to compare it to the unfolding mechanisms caused either by mechanical or thermal perturbations. We show that each perturbation probes a specific weakness of the protein and causes the disruption of the native fold along different unfolding pathways. Notably, the shear flow and the thermal unfolding exhibit very similar pathways, while because of the directionality of the perturbation, the unfolding under force is quite different. For force and thermal disruption of the native state, the coarse-grained simulations are compared to all-atom simulations in explicit solvent, showing an excellent agreement in the explored unfolding mechanisms. These findings encourage the use of LBMD based on the OPEP model to investigate how a flow can affect the function of larger proteins, for example, in catch-bond systems.

}, doi = {10.1021/acs.jpcb.8b08711}, author = {Languin-Catto{\"e}n, Olivier and Melchionna, Simone and Philippe Derreumaux and Guillaume Stirnemann and Sterpone, Fabio} } @article {2018|2090, title = {Water permeation across artificial I-quartet membrane channels: from structure to disorder.}, journal = {Faraday Discuss}, volume = {209}, year = {2018}, month = {2018 09 28}, pages = {125-148}, abstract = {

Artificial water channels (AWCs) have been designed for water transport across membranes with the aim to mimic the high water permeability observed for biological systems such as aquaporins (\∼108-109 water molecules per s per channel), as well as their selectivity to reject ion permeation at the same time. Recent works on designed self-assembling alkylureido-ethylimidazole compounds forming imidazole-quartet channels (I-quartets), have shown both high water permeability and total ionic-rejection. I-quartets are thus promising candidates for further development of AWCs. However, the molecular mechanism of water permeation as well as I-quartet organization and stability in a membrane environment need to be fully understood to guide their optimal design. Here, we use a wide range of all-atom molecular dynamics (MD) simulations and their analysis to understand the structure/activity relationships of the I-quartet channels. Four different types with varying alkyl chain length or chirality have been studied in a complex fully hydrated lipid bilayer environment at both microsecond and nanosecond scale. Microsecond simulations show two distinct behaviors; (i) two out of four systems maintain chiral dipolar oriented water wires, but also undergo a strong reorganization of the crystal shape, (ii) the two other I-quartet channels completely lose the initial organization, nonetheless keeping a water transport activity. Short MD simulations with higher time resolution were conducted to characterize the dynamic properties of water molecules in these model channels and provided a detailed hypothesis on the molecular mechanism of water permeation. The ordered confined water was characterized with quantitative measures of hydrogen-bond life-time and single particle dynamics, showing variability among I-quartet channels. We will further discuss the underlying assumptions, currently based on self-aggregation simulations and crystal patches embedded in lipid bilayer simulations and attempt to describe possible alternative approaches to computationally capture the water permeation mechanism and the self-assembly process of these AWCs.

}, issn = {1364-5498}, doi = {10.1039/c8fd00046h}, author = {Murail, Samuel and Vasiliu, Tudor and Neamtu, Andrei and Barboiu, Mihail and Sterpone, Fabio and Marc Baaden} } @article {2017|2025, title = {Critical structural fluctuations of proteins upon thermal unfolding challenge the Lindemann criterion}, journal = {Proc Natl Acad Sci U S A}, volume = {114}, year = {2017}, month = {Aug}, pages = {9361-9366}, abstract = {

Internal subnanosecond timescale motions are key for the function of proteins, and are coupled to the surrounding solvent environment. These fast fluctuations guide protein conformational changes, yet their role for protein stability, and for unfolding, remains elusive. Here, in analogy with the Lindemann criterion for the melting of solids, we demonstrate a common scaling of structural fluctuations of lysozyme protein embedded in different environments as the thermal unfolding transition is approached. By combining elastic incoherent neutron scattering and advanced molecular simulations, we show that, although different solvents modify the protein melting temperature, a unique dynamical regime is attained in proximity of thermal unfolding in all solvents that we tested. This solvation shell-independent dynamical regime arises from an equivalent sampling of the energy landscape at the respective melting temperatures. Thus, we propose that a threshold for the conformational entropy provided by structural fluctuations of proteins exists, beyond which thermal unfolding is triggered.

}, keywords = {cell thermal stability, Lindemann criterion, Molecular Dynamics Simulation, neutron scattering, protein dynamics}, doi = {10.1073/pnas.1707357114}, author = {Katava, Marina and Guillaume Stirnemann and Zanatta, Marco and Capaccioli, Simone and Pachetti, Maria and Ngai, K L and Sterpone, Fabio and Paciaroni, Alessandro} } @article {2017|2023, title = {Mechanics of Protein Adaptation to High Temperatures}, journal = {J Phys Chem Lett}, volume = {8}, year = {2017}, month = {Dec}, pages = {5884-5890}, abstract = {

Inspired by Somero\&$\#$39;s corresponding state principle that relates protein enhanced thermal stability with mechanical rigidity, we deployed state of the art computational techniques (based on atomistic steered molecular dynamics and Hamiltonian-replica exchange simulations) to study the in silico realization of mechanical and thermal unfolding of two homologous Csp proteins that have evolved to thrive in different thermal environments. By complementing recent single-molecule experiments, we unambiguously show that, for these homologues whose structures are very similar, the increased thermal resistance of the thermophilic variant is not associated with an increased mechanical stability. Our approach provides microscopic insights that are otherwise inaccessible to experimental techniques, and explains why the protein weak spots for thermal and mechanical denaturation are distinct.

}, doi = {10.1021/acs.jpclett.7b02611}, author = {Guillaume Stirnemann and Sterpone, Fabio} } @article {2017|2029, title = {Multi-scale simulations of biological systems using the OPEP coarse-grained model.}, journal = {Biochem Biophys Res Commun}, year = {2017}, month = {2017 Sep 14}, abstract = {

Biomolecules are complex machines that are optimized by evolution to properly fulfill or contribute to a variety of biochemical tasks in the cellular environment. Computer simulations based on quantum mechanics and atomistic force fields have been proven to be a powerful microscope for obtaining valuable insights into many biological, physical, and chemical processes. Many interesting phenomena involve, however, a time scale and a number of degrees of freedom, notably if crowding is considered, that cannot be explored at an atomistic resolution. To bridge the gap between reality and simulation, many different advanced computational techniques and coarse-grained (CG) models have been developed. Here, we report some applications of the CG OPEP protein model to amyloid fibril formation, the response of catch-bond proteins to two types of fluid flow, and interactive simulations to fold peptides with well-defined 3D structures or with intrinsic disorder.

}, issn = {1090-2104}, doi = {10.1016/j.bbrc.2017.08.165}, author = {Sterpone, Fabio and Doutreligne, S{\'e}bastien and Tran, Thanh Thuy and Melchionna, Simone and Marc Baaden and Phuong Hoang Nguyen and Philippe Derreumaux} } @article {2017|2030, title = {Why Is Research on Amyloid-β Failing to Give New Drugs for Alzheimer{\textquoteright}s Disease?}, journal = {ACS Chem Neurosci}, volume = {8}, year = {2017}, month = {2017 Jul 19}, pages = {1435-1437}, abstract = {

The two hallmarks of Alzheimer\&$\#$39;s disease (AD) are the presence of neurofibrillary tangles (NFT) made of aggregates of the hyperphosphorylated tau protein and of amyloid plaques composed of amyloid-β (Aβ) peptides, primarily Aβ1-40 and Aβ1-42. Targeting the production, aggregation, and toxicity of Aβ with small molecule drugs or antibodies is an active area of AD research due to the general acceptance of the amyloid cascade hypothesis, but thus far all drugs targeting Aβ have failed. From a review of the recent literature and our own experience based on in vitro, in silico, and in vivo studies, we present some reasons to explain this repetitive failure.

}, keywords = {Alzheimer Disease, Amyloid beta-Peptides, Animals, Drug Discovery, Humans, Neuroprotective Agents}, issn = {1948-7193}, doi = {10.1021/acschemneuro.7b00188}, author = {Doig, Andrew J and Del Castillo-Frias, Maria P and Berthoumieu, Olivia and Tarus, Bogdan and Nasica-Labouze, Jessica and Sterpone, Fabio and Phuong Hoang Nguyen and Hooper, Nigel M and Faller, Peter and Philippe Derreumaux} } @article {2016|1656, title = {Coarse-grained and All-atom Simulations towards the Early and Late Steps of Amyloid Fibril Formation}, journal = {Isr. J. Chem.}, volume = {DOI: 10.1002/ijch.201600048.}, year = {2016}, author = {M. Chiricotto and Thanh-Thuy Tran and Phuong Hoang Nguyen and S. Melchionna and Fabio Sterpone and Philippe Derreumaux} } @article {2016|1712, title = {Dimerization Mechanism of Alzheimer A beta(40) Peptides: The High Content of Intrapeptide-Stabilized Conformations in A2V and A2T Heterozygous Dimers Retards Amyloid Fibril Formation}, journal = {J. Phys. Chem. B}, volume = {120}, number = {47}, year = {2016}, pages = {12111{\textendash}12126}, abstract = {Amyloid beta (A beta) oligomerization is associated with the origin and progression of Alzheimer{\textquoteright}s disease (AD). While the A2V mutation enhances aggregation kinetics and toxicity, mixtures of wild-type (WT) and A2V, and also WT and A2T, peptides retard fibril formation and protect against AD. In this study, we simulate the equilibrium ensemble of WT:A2T A beta(40) dimer by means of extensive atomistic replica exchange molecular dynamics and compare our results with previous equivalent simulations of A2V:A2V, WT:WT, and WT:A2V A beta(40) dimers for a total time scale of nearly 0.1 ms. Qualitative comparison of the resulting thermodynamic properties, such as the relative binding free energies, with the reported experimental kinetic and thermodynamic data affords us important insight into the conversion from slow-pathway to fast-pathway dimer conformations. The crucial reaction coordinate or driving force of such transformation turns out to be related to hydrophobic interpeptide interactions. Analysis of the equilibrium ensembles shows that the fast-pathway conformations contain interpeptide out-of-register antiparallel beta-sheet structures at short interpeptide distances. In contrast, the slow-pathway conformations are formed by the association of peptides at large interpeptide distances and high intrapeptide compactness, such as conformations containing intramolecular three-stranded beta-sheets which sharply distinguish fast (A2V:A2V and WT:WT) and slow (WT:A2T and WT:A2V) amyloid-forming sequences. Also, this analysis leads us to predict that a molecule stabilizing the intramolecular three-stranded beta-sheet or inhibiting the formation of an interpeptide beta-sheet spanning residues 17-20 and 31-37 would further reduce fibril formation and probably the cytotoxicity of A beta species.}, issn = {1520-6106}, doi = {10.1021/acs.jpcp.6b10722}, author = {Phuong Hoang Nguyen and Fabio Sterpone and Pouplana, Ramon and Philippe Derreumaux and Campanera, Josep M.} } @conference {2016|1607, title = {Hydrodynamic Effects on Amyloid-beta Aggregation}, booktitle = {Biophys. J.}, volume = {110}, number = {3, 1}, year = {2016}, note = {60th Annual Meeting of the Biophysical-Society, Los Angeles, CA, FEB 27-MAR 02, 2016}, month = {feb}, pages = {219A}, publisher = {Biophys Soc}, organization = {Biophys Soc}, issn = {0006-3495}, author = {Chiricotto, Mara and Melchionna, Simone and Philippe Derreumaux and Fabio Sterpone} } @article {2016|1702, title = {Hydrodynamic effects on beta-amyloid (16-22) peptide aggregation}, journal = {J. Chem. Phys.}, volume = {145}, number = {3}, year = {2016}, month = {jul}, abstract = {Computer simulations based on simplified representations are routinely used to explore the early steps of amyloid aggregation. However, when protein models with implicit solvent are employed, these simulations miss the effect of solvent induced correlations on the aggregation kinetics and lifetimes of metastable states. In this work, we apply the multi-scale Lattice Boltzmann Molecular Dynamics technique (LBMD) to investigate the initial aggregation phases of the amyloid A beta(16-22) peptide. LBMD includes naturally hydrodynamic interactions (HIs) via a kinetic on-lattice representation of the fluid kinetics. The peptides are represented by the flexible OPEP coarse-grained force field. First, we have tuned the essential parameters that control the coupling between the molecular and fluid evolutions in order to reproduce the experimental diffusivity of elementary species. The method is then deployed to investigate the effect of HIs on the aggregation of 100 and 1000 A beta(16-22) peptides. We show that HIs clearly impact the aggregation process and the fluctuations of the oligomer sizes by favouring the fusion and exchange dynamics of oligomers between aggregates. HIs also guide the growth of the leading largest cluster. For the 100 A beta(16-22) peptide system, the simulation of similar to 300 ns allowed us to observe the transition from ellipsoidal assemblies to an elongated and slightly twisted aggregate involving almost the totality of the peptides. For the 1000 A beta(16-22) peptides, a system of unprecedented size at quasi-atomistic resolution, we were able to explore a branched disordered fibril-like structure that has never been described by other computer simulations, but has been observed experimentally. Published by AIP Publishing.}, issn = {0021-9606}, doi = {10.1063/1.4958323}, author = {Chiricotto, Mara and Melchionna, Simone and Philippe Derreumaux and Fabio Sterpone} } @article {2016|1578, title = {Impact of the A2V Mutation on the Heterozygous and Homozygous A beta 1-40 Dimer Structures from Atomistic Simulations}, journal = {Acs Chem. Neurosci.}, volume = {7}, number = {6}, year = {2016}, month = {jun}, pages = {823{\textendash}832}, abstract = {The A2V mutation was reported to protect from Alzheimer{\textquoteright}s disease in its heterozygous form and cause an early Alzheimer{\textquoteright}s disease type dementia in its homozygous form. Experiments showed that the aggregation rate follows the order A2V > WT (wild-type) > A2V-WT. To understand the impact of this mutation, we carried out replica exchange molecular dynamics simulations of A beta 1-40 WT-A2V and A2V-A2V dimers and compared to the WT dimer. Our atomistic simulations reveal that the mean secondary structure remains constant, but there are substantial differences in the intramolecular and intermolecular conformations upon single and double A2V mutation. Upon single mutation, the intrinsic disorder is reduced, the intermolecular potential energies are reduced, the population of intramolecular three-stranded beta-sheets is increased, and the number of all a dimer topologies is decreased. Taken together, these results offer an explanation for the reduced aggregation rate of the A beta 1-40 A2V-WT peptides and the protective effect of A2V in heterozygotes.}, issn = {1948-7193}, doi = {10.1021/acschemneuro.6b00053}, author = {Phuong Hoang Nguyen and Fabio Sterpone and Campanera, Josep M. and Nasica-Labouze, Jessica and Philippe Derreumaux} } @article {2016|1735, title = {Multiscale simulation of molecular processes in cellular environments}, journal = {Philosophical Transactions of the Royal Society A-mathematical Physical and Engineering Sciences}, volume = {374}, number = {2080}, year = {2016}, abstract = {We describe the recent advances in studying biological systems via multiscale simulations. Our scheme is based on a coarse-grained representation of the macromolecules and a mesoscopic description of the solvent. The dual technique handles particles, the aqueous solvent and their mutual exchange of forces resulting in a stable and accurate methodology allowing biosystems of unprecedented size to be simulated. This article is part of the themed issue {\textquoteleft}Multiscale modelling at the physics-chemistry-biology interface{\textquoteright}.}, issn = {1364-503X}, doi = {10.1098/rsta.2016.0225}, author = {Chiricotto, Mara and Fabio Sterpone and Philippe Derreumaux and Melchionna, Simone} } @article {2016|1687, title = {Stability and Function at High Temperature. What Makes a Thermophilic GTPase Different from Its Mesophilic Homologue}, journal = {J. Phys. Chem. B}, volume = {120}, year = {2016}, pages = {2721{\textendash}2730}, abstract = {

Comparing homologous enzymes adapted to different thermal environments aids to shed light on their delicate stability/function trade-off. Protein mechanical rigidity was postulated to secure stability and high-temperature functionality of thermophilic proteins. In this work, we challenge the corresponding-state principle for a pair of homologous GTPase domains by performing extensive molecular dynamics simulations, applying conformational and kinetic clustering, as well as exploiting an enhanced sampling technique (REST2). While it was formerly shown that enhanced protein flexibility and high temperature stability can coexist in the apo hyperthermophilic variant, here we focus on the holo states of both homologues by mimicking the enzymatic turnover. We clearly show that the presence of the ligands affects the conformational landscape visited by the proteins, and that the corresponding state principle applies for some functional modes. Namely, in the hyperthermophilic species, the flexibility of the effec...

}, issn = {15205207}, doi = {10.1021/acs.jpcb.6b00306}, author = {Katava, Marina and Kalimeri, Maria and Guillaume Stirnemann and Fabio Sterpone} } @article {2016|1764, title = {Thermal activation of {\textquoteleft}allosteric-like{\textquoteright} large-scale motions in a eukaryotic Lactate Dehydrogenase.}, journal = {Sci. Reports}, volume = {7}, year = {2016}, pages = {41092}, author = {M. Katava and M. Maccarini and G. Villain and A. Paciaroni and M. Sztucki and O. Ivanova and D. Madern and Fabio Sterpone} } @conference {2016|1608, title = {Toward Microscopic Simulations of Proteins in Cell-Like Environments}, booktitle = {Biophys. J.}, volume = {110}, number = {3, 1}, year = {2016}, note = {60th Annual Meeting of the Biophysical-Society, Los Angeles, CA, FEB 27-MAR 02, 2016}, month = {feb}, pages = {386A}, publisher = {Biophys Soc}, organization = {Biophys Soc}, issn = {0006-3495}, author = {Fabio Sterpone and Philippe Derreumaux and Melchionna, Simone} } @article {2016|1633, title = {Water Determines the Structure and Dynamics of Proteins}, journal = {Chem. Rev.}, volume = {116}, year = {2016}, pages = {7673{\textendash}7697}, author = {M-C. Bellissent-Funel and A. Hassanali and M. Havenith and R. Henchman and P. Pohl and Fabio Sterpone and D. van der Spoel and Y. Xu and A. E. Garcia} } @article {2015|1634, title = {Amyloid beta Protein and Alzheimer{\textquoteright}s Disease: When Computer Simulations Complement Experimental Studies}, journal = {Chem. Rev.}, volume = {115}, number = {9}, year = {2015}, month = {may}, pages = {3518{\textendash}3563}, doi = {10.1021/cr500638n}, author = {Nasica-Labouze, Jessica and Phuong Hoang Nguyen and Fabio Sterpone and Berthoumieu, Olivia and Buchete, Nicolae-Viorel and Cote, Sebastien and De Simone, Alfonso and Doig, Andrew J. and Faller, Peter and Garcia, Angel and Laio, Alessandro and Li, Mai Suan and Melchionna, Simone and Mousseau, Normand and Mu, Yuguang and Paravastu, Anant and Pasquali, Samuela and Rosenman, David J. and Strodel, Birgit and Tarus, Bogdan and Viles, John H. and Zhang, Tong and Wang, Chunyu and Philippe Derreumaux} } @article {2015|1910, title = {Are coarse-grained models apt to detect protein thermal stability? The case of \{OPEP\} force field}, journal = {J. Non-cryst. Solids}, volume = {407}, year = {2015}, note = {7th IDMRCS: Relaxation in Complex Systems}, pages = {494{\textendash}501}, keywords = {Conformational substates network}, doi = {10.1016/j.jnoncrysol.2014.07.005}, url = {http://www.sciencedirect.com/science/article/pii/S0022309314002889}, author = {Maria Kalimeri and Philippe Derreumaux and Fabio Sterpone} } @article {2015|1709, title = {Protein Simulations in Fluids: Coupling the OPEP Coarse-Grained Force Field with Hydrodynamics}, journal = {J. Chem. Theory Comput.}, volume = {11}, number = {4}, year = {2015}, month = {apr}, pages = {1843{\textendash}1853}, doi = {10.1021/ct501015h}, author = {Fabio Sterpone and Philippe Derreumaux and Melchionna, Simone} } @article {2015|1677, title = {Recovering protein thermal stability using all-atom Hamiltonian replica-exchange simulations in explicit solvent}, journal = {J. Chem. Theo. Comput.}, volume = {11}, year = {2015}, pages = {5573{\textendash}5577}, abstract = {

The REST2 method is successfully applied to investigate the thermal stability of chignolin CLN025 and of Trp-cage. As opposed to temperature replica exchange, REST2 relies on the rescaling of the protein potential energy, which allows a smaller number of replicas. The shape of the stability curve reconstructed on the basis of the corresponding-state principle is in very good agreement with experimental data; for chignolin, the effect of mutations is also recovered.

}, issn = {15499626}, doi = {10.1021/acs.jctc.5b00954}, author = {Guillaume Stirnemann and Fabio Sterpone} } @article {2015|1668, title = {Role of Internal Water on Protein Thermal Stability: The Case of Homologous G Domains.}, journal = {J. Phys. Chem. B}, volume = {119}, year = {2015}, month = {jul}, pages = {8939{\textendash}49}, abstract = {

In this work, we address the question of whether the enhanced stability of thermophilic proteins has a direct connection with internal hydration. Our model systems are two homologous G domains of different stability: the mesophilic G domain of the elongation factor thermal unstable protein from E. coli and the hyperthermophilic G domain of the EF-1α protein from S. solfataricus. Using molecular dynamics simulation at the microsecond time scale, we show that both proteins host water molecules in internal cavities and that these molecules exchange with the external solution in the nanosecond time scale. The hydration free energy of these sites evaluated via extensive calculations is found to be favorable for both systems, with the hyperthermophilic protein offering a slightly more favorable environment to host water molecules. We estimate that, under ambient conditions, the free energy gain due to internal hydration is about 1.3 kcal/mol in favor of the hyperthermophilic variant. However, we also find that, at the high working temperature of the hyperthermophile, the cavities are rather dehydrated, meaning that under extreme conditions other molecular factors secure the stability of the protein. Interestingly, we detect a clear correlation between the hydration of internal cavities and the protein conformational landscape. The emerging picture is that internal hydration is an effective observable to probe the conformational landscape of proteins. In the specific context of our investigation, the analysis confirms that the hyperthermophilic G domain is characterized by multiple states and it has a more flexible structure than its mesophilic homologue.

}, issn = {1520-5207}, doi = {10.1021/jp507571u}, author = {Rahaman, Obaidur and Kalimeri, Maria and Melchionna, Simone and J{\'e}r{\^o}me H{\'e}nin and Fabio Sterpone} } @article {2015|1769, title = {Stay Wet, Stay Stable? How Internal Water Helps the Stability of Thermophilic Proteins}, journal = {The Journal of Physical Chemistry B}, volume = {119}, number = {40}, year = {2015}, pages = {12760{\textendash}12770}, publisher = {American Chemical Society}, author = {Chakraborty, Debashree and Antoine Taly and Fabio Sterpone} } @article {2015|1714, title = {Structures of the Alzheimer{\textquoteright}s Wild-Type A beta 1-40 Dimer from Atomistic Simulations}, journal = {J. Phys. Chem. B}, volume = {119}, number = {33}, year = {2015}, pages = {10478{\textendash}10487}, doi = {10.1021/acs.jpcb.5b05593}, author = {Tarus, Bogdan and Thanh-Thuy Tran and Nasica-Labouze, Jessica and Fabio Sterpone and Phuong Hoang Nguyen and Philippe Derreumaux} } @article {2014|1964, title = {Interface Matters: The Stiffness Route to Stability of a Thermophilic Tetrameric Malate Dehydrogenase}, journal = {Plos One}, volume = {9}, number = {12}, year = {2014}, month = {dec}, pages = {e113895}, url = {http://dx.doi.org/10.1371\%2Fjournal.pone.0113895}, author = {Kalimeri, Maria and Girard, Eric and Madern, Dominique and Sterpone, Fabio} } @article {2013|1797, title = {Biomolecular hydration dynamics: a jump model perspective}, journal = {Chem. Soc. Rev.}, volume = {42}, number = {13}, year = {2013}, pages = {5672{\textendash}5683}, author = {Fogarty, Aoife C. and Elise Dubou{\'e}-Dijon and Sterpone, Fabio and Hynes, James T. and Laage, Damien} } @article {2013|1926, title = {How Conformational Flexibility Stabilizes the Hyperthermophilic Elongation Factor G-Domain}, journal = {J. Phys. Chem. B}, volume = {117}, number = {44}, year = {2013}, month = {nov}, pages = {13775{\textendash}13785}, author = {Kalimeri, Maria and Rahaman, Obaidur and Melchionna, Simone and Sterpone, Fabio} } @article {2013|1892, title = {Importance of the Ion-Pair Interactions in the OPEP Coarse-Grained Force Field: Parametrization and Validation}, journal = {J. Chem. Theory Comput.}, volume = {9}, number = {10}, year = {2013}, month = {oct}, pages = {4574{\textendash}4584}, doi = {10.1021/ct4003493}, author = {Sterpone, Fabio and Phuong Hoang Nguyen and Kalimeri, Maria and Philippe Derreumaux} } @inbook {2013|1533, title = {Inquiring Protein Thermostability: Is Resistance to Temperature Stress a Rigidity/Flexibility Trade-off?}, booktitle = {Proceedings of the European Conference on Complex Systems 2012}, year = {2013}, publisher = {Springer International Publishing}, organization = {Springer International Publishing}, author = {Kalimeri, Maria and Melchionna, Simone and Sterpone, Fabio} } @article {2012|1554, title = {Early Stage of the Dehydrogenation of NaAlH4 by Ab Initio Rare Event Simulations}, journal = {The Journal of Physical Chemistry C}, volume = {116}, number = {37}, year = {2012}, pages = {19636{\textendash}19643}, doi = {10.1021/jp3019588}, author = {Sterpone, Fabio and Bonella, Sara and Meloni, Simone} } @article {2012|1488, title = {Magnitude and molecular origin of water slowdown next to a protein}, journal = {J. Am. Chem. Soc.}, volume = {134}, year = {2012}, pages = {4116{\textendash}4119}, abstract = {

Hydration shell dynamics plays a critical role in protein folding and biochemical activity and has thus been actively studied through a broad range of techniques. While all observations concur with a slowdown of water dynamics relative to the bulk, the magnitude and molecular origin of this retardation remain unclear. Via numerical simulations and theoretical modeling, we establish a molecular description of protein hydration dynamics and identify the key protein features that govern it. Through detailed microscopic mapping of the water reorientation and hydrogen-bond (HB) dynamics around lysozyme, we first determine that 80\% of the hydration layer waters experience a moderate slowdown factor of \~{}2-3, while the slower residual population is distributed along a power-law tail, in quantitative agreement with recent NMR results. We then establish that the water reorientation mechanism at the protein interface is dominated by large angular jumps similar to the bulk situation. A theoretical extended jump model is shown to provide the first rigorous determination of the two key contributions to the observed slowdown: a topological excluded-volume factor resulting from the local protein geometry, which governs the dynamics of the fastest 80\% of the waters, and a free energetic factor arising from the water-protein HB strength, which is especially important for the remaining waters in confined sites at the protein interface. These simple local factors are shown to provide a nearly quantitative description of the hydration shell dynamics.

}, issn = {00027863}, author = {Fabio Sterpone and Guillaume Stirnemann and Laage, Damien} } @article {2012|1995, title = {Structural and Spectroscopic Properties of Water around Small Hydrophobic Solutes}, journal = {The Journal of Physical Chemistry B}, volume = {116}, number = {38}, year = {2012}, pages = {11695{\textendash}11700}, doi = {10.1021/jp303213m}, author = {Montagna, Maria and Sterpone, Fabio and Guidoni, Leonardo} } @article {2012|1795, title = {Thermophilic proteins: insight and perspective from in silico experiments}, journal = {Chem. Soc. Rev.}, volume = {41}, year = {2012}, pages = {1665{\textendash}1676}, publisher = {The Royal Society of Chemistry}, abstract = {Proteins from thermophilic and hyperthermophilic organisms are stable and function at high temperatures (50-100 [degree]C). The importance of understanding the microscopic mechanisms underlying this thermal resistance is twofold: it is key for acquiring general clues on how proteins maintain their fold stable and for targeting those medical and industrial applications that aim at designing enzymes that can work under harsh conditions. In this tutorial review we first provide the general background of protein thermostability by specifically focusing on the structural and thermodynamic peculiarities; next{,} we discuss how computational studies based on Molecular Dynamics simulations can broaden and refine our knowledge on such special class of proteins.}, author = {Sterpone, Fabio and Melchionna, Simone} } @article {2012, title = {Water Jump Reorientation: From Theoretical Prediction to Experimental Observation}, journal = {Acc. Chem. Res.}, volume = {45}, number = {1}, year = {2012}, pages = {53{\textendash}62}, doi = {10.1021/ar200075u}, author = {Laage, Damien and Guillaume Stirnemann and Sterpone, Fabio and Hynes, James T.} } @article {2011|1771, title = {Coherent Excitation Transfer Driven by Torsional Dynamics: a Model Hamiltonian for PPV Type Systems}, journal = {Zeitschrift F{\"u}r Physikalische Chemie}, volume = {255}, year = {2011}, pages = {541{\textendash}551}, author = {Fabio Sterpone and R. Martinazzo and A.N. Panda and I. Burghardt} } @article {2011|1690, title = {Dynamics of water in concentrated solutions of amphiphiles: Key roles of local structure and aggregation}, journal = {J. Phys. Chem. B}, volume = {115}, year = {2011}, pages = {3254{\textendash}3262}, abstract = {

Water translational and reorientational dynamics in concentrated solutions of amphiphiles are investigated through molecular dynamics simulations and analytic modeling. We evidence the critical importance of the solute concentration in determining the magnitude of the slowdown in water dynamics compared to the bulk situation. The comparison of concentrated aqueous solutions of tetramethylurea, which tends to aggregate, and of trimethylamine N-oxide, which does not, shows the dramatic impact of solute clustering on the water dynamics. No significant decoupling of the reorientation and translation dynamics of water is observed, even at very high solute concentrations. The respective roles of energetic and topological disorders in determining the translational subdiffusive water dynamics in these confining environments are discussed. The water reorientational dynamics is shown to be quantitatively described by an extended jump model which combines two factors determined by the local structure: the transition-state excluded volume and the transition-state hydrogen-bond strength.

}, issn = {15206106}, author = {Guillaume Stirnemann and Fabio Sterpone and Laage, Damien} } @article {2011|1383, title = {Reorientation and Allied Dynamics in Water and Aqueous Solutions}, journal = {Annu. Rev. Phys. Chem.}, volume = {62}, year = {2011}, pages = {395{\textendash}416}, abstract = {

The reorientation of a water molecule is important for a host of phenomena, ranging over?in an only partial listing?the key dynamic hydrogen-bond network restructuring of water itself, aqueous solution chemical reaction mechanisms and rates, ion transport in aqueous solution and membranes, protein folding, and enzymatic activity. This review focuses on water reorientation and related dynamics in pure water, and for aqueous solutes with hydrophobic, hydrophilic, and amphiphilic character, ranging from tetramethylurea to halide ions and amino acids. Attention is given to the application of theory, simulation, and experiment in the probing of these dynamics, in usefully describing them, and in assessing the description. Special emphasis is placed on a novel sudden, large-amplitude jump mechanism for water reorientation, which contrasts with the commonly assumed Debye rotational diffusion mechanism, characterized by small-amplitude angular motion. Some open questions and directions for further research are also discussed. Expected final online publication date for the Annual Review of Physical Chemistry Volume 62 is March 31, 2011. Please see http://www.annualreviews.org/catalog/pubdates.aspx for revised estimates.

}, isbn = {0066-426X 1545-1593}, issn = {0066-426X}, doi = {doi: 10.1146/annurev.physchem.012809.103503}, url = {http://www.annualreviews.org/doi/abs/10.1146/annurev.physchem.012809.103503$\backslash$nhttp://www.annualreviews.org.login.ezproxy.lib.purdue.edu/doi/pdf/10.1146/annurev.physchem.012809.103503}, author = {Laage, Damien and Guillaume Stirnemann and Fabio Sterpone and Rey, Rossend and Hynes, James T.} } @inbook {2011|1773, title = {Role of packing, hydration and fluctuation on Thermostability}, booktitle = {Thermostable Proteins Structural Stability and Design}, year = {2011}, publisher = {CRC Press - Taylor and Francis}, organization = {CRC Press - Taylor and Francis}, author = {Fabio Sterpone and Simone Melchionna}, editor = {Srikanta Sen and Lennart Nilsson} } @article {2010|1685, title = {Non adiabatic simulations of exciton dissociation in poly-p-phenylenevinylene oligomers}, journal = {J. Phys. Chem. A}, volume = {114}, year = {2010}, pages = {7661{\textendash}7670}, author = {M. Bedard-Hearn and Fabio Sterpone and P.J. Rossky} } @article {2010|1445, title = {Water around thermophilic proteins: the role of charged and apolar atoms}, journal = {J Phys: Cond Matt}, volume = {22}, number = {28}, year = {2010}, pages = {284113}, author = {Fabio Sterpone and Claudia Bertonati and Giuseppe Briganti and Simone Melchionna} } @article {2010|1832, title = {Water hydrogen-bond dynamics around amino acids: the key role of hydrophilic hydrogen-bond acceptor groups}, journal = {J. Phys. Chem. B}, volume = {114}, number = {5}, year = {2010}, pages = {2083{\textendash}9}, abstract = {

Water hydrogen-bond (HB) dynamics around amino acids in dilute aqueous solution is investigated through molecular dynamics simulations and analytic modeling. We especially highlight the critical role played by hydrophilic HB acceptors: the strength of the HB formed with water has a pronounced effect on the HB dynamics, in accord with several experimental observations. In contrast, we evidence that hydrophilic HB donors induce a moderate slowdown in the water HB exchange dynamics due to an excluded volume effect, similar to that of hydrophobic groups. We present an analytic model which rationalizes the effect of all examined amino acid sites on the HB dynamics and whose predictions are in excellent agreement with the numerical simulations. This model provides the acceleration or retardation in the HB exchange time with respect to the bulk through the combination of the solute excluded volume factor with the solute-water HB strength factor, both referring to the HB exchange transition state.

}, author = {Sterpone, Fabio and Guillaume Stirnemann and Hynes, James T and Laage, Damien} } @article {2009|1831, title = {Key role of proximal water in regulating thermostable proteins}, journal = {J. Phys. Chem. B}, volume = {113}, number = {1}, year = {2009}, month = {jan}, pages = {131{\textendash}7}, abstract = {Three homologous proteins with mesophilic, thermophilic and hyperthermophilic character have been studied via molecular dynamics simulations at four different temperatures in order to investigate how water controls thermostability. The water-exposed surface of the protein is shown to increase with the degree of thermophilicity, and the role of water in enhancing the protein internal flexibility and structural robustness is elucidated. The presence of water-water hydrogen bond clusters enveloping the macromolecule is shown to correlate with thermal robustness when going from the mesophilic to the hyperthermophilic variants. Our analysis indicates that essential contributions to thermostability stem from protein-water surface effects whereas the protein internal packing plays a minor role.}, doi = {10.1021/jp805199c}, author = {Sterpone, Fabio and Bertonati, Claudia and Briganti, Giuseppe and Melchionna, Simone} } @article {2009|1440, title = {Nonadiabatic mixed quantum-classical dynamic simulation of pi-stacked oligophenylenevinylenes}, journal = {J. Phys. Chem. A}, volume = {113}, number = {15}, year = {2009}, pages = {3427{\textendash}30}, author = {Sterpone, Fabio and Bedard-Hearn, Michael J and Rossky, Peter J} } @article {2009|1495, title = {Sphere versus cylinder: the effect of packing on the structure of nonionic C12E6 micelles}, journal = {Langmuir}, volume = {25}, number = {16}, year = {2009}, pages = {8960{\textendash}7}, author = {Sterpone, Fabio and Briganti, G and Pierleoni, C} } @article {2008|1434, title = {Dissecting the Hydrogen Bond: A Quantum Monte Carlo Approach}, journal = {J Chem Theo Comp}, volume = {4}, number = {9}, year = {2008}, pages = {1428{\textendash}1434}, author = {Sterpone, Fabio and Spanu, Leonardo and Ferraro, Luca and Sorella, Sandro and Guidoni, Leonardo} } @article {2008|1829, title = {Molecular modeling and simulation of conjugated polymer oligomers: ground and excited state chain dynamics of PPV in the gas phase}, journal = {J. Phys. Chem. B}, volume = {112}, number = {16}, year = {2008}, pages = {4983{\textendash}93}, author = {Sterpone, Fabio and Rossky, Peter J} } @article {2008|1494, title = {Pressure-induced core packing and interfacial dehydration in nonionic C12E6 micelle in aqueous solution}, journal = {Langmuir}, volume = {24}, number = {12}, year = {2008}, pages = {6067{\textendash}71}, author = {Sterpone, Fabio and Briganti, G and Melchionna, S and Pierleoni, C} } @article {2008|1678, title = {Water-water hydrogen bond studied by QMC}, journal = {J. Chem. Theory. Comput.}, volume = {4}, year = {2008}, pages = {1428{\textendash}1432}, author = {Fabio Sterpone and L. Spanu and L. Ferraro and S. Sorella and L. Guidoni} } @article {2007|1828, title = {How protein surfaces induce anomalous dynamics of hydration water}, journal = {J. Phys. Chem. B}, volume = {111}, number = {26}, year = {2007}, pages = {7584{\textendash}90}, abstract = {Water around biomolecules slows down with respect to pure water, and both rotation and translation exhibit anomalous time dependence in the hydration shell. The origin of such behavior remains elusive. We use molecular dynamics simulations of water dynamics around several designed protein models to establish the connection between the appearance of the anomalous dynamics and water-protein interactions. For the first time we quantify the separate effect of protein topological and energetic disorder on the hydration water dynamics. When a static protein structure is simulated, we show that both types of disorder contribute to slow down water diffusion, and that allowing for protein motion, increasing the spatial dimensionality of the interface, reduces the anomalous character of hydration water. The rotation of water is, instead, altered by the energetic disorder only; indeed, when electrostatic interactions between the protein and water are switched off, water reorients even faster than in the bulk. The dynamics of water is also related to the collective structure{\textendash}{\`a} voir the hydrogen bond (H-bond) network{\textendash}formed by the solvent enclosing the protein surface. We show that, as expected for a full hydrated protein, when the protein surface offers pinning sites (charged or polar sites), the superficial water-water H-bond network percolates throughout the whole surface, hindering the water diffusion, whereas it does not when the protein surface lacks electrostatic interactions with water and the water diffusion is enhanced.}, author = {Pizzitutti, Francesco and Marchi, Massimo and Sterpone, Fabio and Rossky, Peter J} } @article {2006|1441, title = {Molecular modeling and simulation of water near model micelles: diffusion, rotational relaxation and structure at the hydration interface}, journal = {J. Phys. Chem. B}, volume = {110}, number = {23}, year = {2006}, pages = {11504{\textendash}10}, author = {Sterpone, Fabio and Marchetti, Gino and Pierleoni, Carlo and Marchi, Massimo} } @article {2006|1827, title = {Structure and dynamics of hydrogen bonds in the interface of a C12E6 spherical micelle in water solution: a MD study at various temperatures}, journal = {J. Phys. Chem. B}, volume = {110}, number = {37}, year = {2006}, pages = {18254{\textendash}61}, author = {Sterpone, Fabio and Pierleoni, Carlo and Briganti, Giuseppe and Marchi, Massimo} } @article {2005|1400, title = {Hydration and thermodynamic equilibrium of non-ionic surfactant in solution}, journal = {Coll Surf A}, volume = {261}, year = {2005}, pages = {93{\textendash}99}, author = {Briganti, Giuseppe and D{\textquoteright}arrigo, Giovanni and Maccarini, Marco and Pierleoni, Carlo and Sterpone, Fabio} } @article {2004|1493, title = {Molecular dynamics study of temperature dehydration of a C12E6 spherical micelle}, journal = {Langmuir}, volume = {20}, number = {11}, year = {2004}, pages = {4311{\textendash}4}, author = {Sterpone, Fabio and Pierleoni, Carlo and Briganti, Giuseppe and Marchit, Massimo} } @article {2004|1826, title = {Molecular Modeling and Simulations of AOT{\^a}{\textasciicircum}{\textquoteright}Water Reverse Micelles in Isooctane:{\^a}{\texteuro}{\textperthousand} Structural and Dynamic Properties}, journal = {J. Phys. Chem. B}, volume = {108}, number = {50}, year = {2004}, pages = {19458{\textendash}19466}, author = {Abel, St{\'e}phane and Sterpone, Fabio and Bandyopadhyay, Sanjoy and Marchi, Massimo} } @article {2004|1718, title = {Temperature dehydration of C12E6 micelle}, journal = {Langmuir}, volume = {20}, year = {2004}, pages = {4311{\textendash}4314}, author = {Fabio Sterpone and C. Pierleoni and G. Briganti and M. Marchi} } @article {2003|1694, title = {Linear response and electron transfer in complex biomolecules systems and Reaction Center Protein}, journal = {J. Phys. Chem. B}, volume = {107}, year = {2003}, pages = {11208{\textendash}11215}, author = {Fabio Sterpone and M. Ceccarelli and M. Marchi} } @article {2002|1817, title = {Water rotational relaxation and diffusion in hydrated lysozyme}, journal = {J. Am. Chem. Soc.}, volume = {124}, number = {23}, year = {2002}, month = {jun}, pages = {6787{\textendash}91}, abstract = {This paper is concerned with the dynamics of water around a small globular protein. Dipolar second-rank relaxation time and diffusion properties of surface water were computed by extensive molecular dynamics simulations of lysozyme in water which lasted a total of 28 ns. Our results indicate that the rotational relaxation of water in the vicinity of lysozyme is 3-7 times slower than that in the bulk depending on how the hydration shell is defined in the calculation. We have also verified that the dynamics of water translational diffusion in the vicinity of lysozyme have retardations similar to rotational relaxation. This is a common assumption in nuclear magnetic relaxation dispersion (NMRD) studies to derive residence times. In contrast to bulk water dynamics, surface water is in a dispersive diffusion regime or subdiffusion. Very good agreement of dipolar second-rank relaxation time with NMRD estimates is obtained by using appropriate dimensions of the hydration shell. Although our computed second-rank dipolar retardations are independent of the water model, SPC/E describes more realistically the time scale of the water dynamics around lysozyme than does TIP3P.}, author = {Marchi, Massimo and Sterpone, Fabio and Ceccarelli, Matteo} } @article {2001|1933, title = {Molecular Dynamics Study of Spherical Aggregates of Chain Molecules at Different Degrees of Hydrophilicity in Water Solution}, journal = {Langmuir}, volume = {17}, number = {16}, year = {2001}, pages = {5103{\textendash}5110}, author = {Sterpone, Fabio and Briganti, Giuseppe and Pierleoni, Carlo} }