@article {2017|2028,
	title = {New Coarse Variables for the Accurate Determination of Standard Binding Free Energies},
	journal = {J Chem Theory Comput},
	volume = {13},
	year = {2017},
	month = {2017 Nov 14},
	pages = {5173-5178},
	abstract = {<p>To improve sampling of the configurational entropy change upon protein-ligand binding, we have introduced a new set of coarse variables describing the relative orientation and position of the ligand via a global macromolecular orientational procedure, onto which geometrical restraints are applied. Evaluating the potential of mean force for the different coarse variables, the experimental standard binding free energy for three decapeptides associated with the SH3 domain of the Abl kinase is reproduced quantitatively.</p>
},
	issn = {1549-9626},
	doi = {10.1021/acs.jctc.7b00791},
	author = {Fu, Haohao and Cai, Wensheng and J{\'e}r{\^o}me H{\'e}nin and Roux, Beno{\^\i}t and Chipot, Christophe}
}
@article {2016|1672,
	title = {A Novel Bifunctional Alkylphenol Anesthetic Allows Characterization of gamma-Aminobutyric Acid, Type A (GABAA), Receptor Subunit Binding Selectivity in Synaptosomes.},
	journal = {J. Biol. Chem},
	volume = {291},
	year = {2016},
	month = {sep},
	pages = {20473{\textendash}86},
	abstract = {<p>Propofol, an intravenous anesthetic, is a positive modulator of the GABAA receptor, but the mechanistic details, including the relevant binding sites and alternative targets, remain disputed. Here we undertook an in-depth study of alkylphenol-based anesthetic binding to synaptic membranes. We designed, synthesized, and characterized a chemically active alkylphenol anesthetic (2-((prop-2-yn-1-yloxy)methyl)-5-(3-(trifluoromethyl)-3H-diazirin-3-yl)phenol, AziPm-click (1)), for affinity-based protein profiling (ABPP) of propofol-binding proteins in their native state within mouse synaptosomes. The ABPP strategy captured approximately 4\% of the synaptosomal proteome, including the unbiased capture of five alpha or beta GABAA receptor subunits. Lack of gamma2 subunit capture was not due to low abundance. Consistent with this, independent molecular dynamics simulations with alchemical free energy perturbation calculations predicted selective propofol binding to interfacial sites, with higher affinities for alpha/beta than gamma-containing interfaces. The simulations indicated hydrogen bonding is a key component leading to propofol-selective binding within GABAA receptor subunit interfaces, with stable hydrogen bonds observed between propofol and alpha/beta cavity residues but not gamma cavity residues. We confirmed this by introducing a hydrogen bond-null propofol analogue as a protecting ligand for targeted-ABPP and observed a lack of GABAA receptor subunit protection. This investigation demonstrates striking interfacial GABAA receptor subunit selectivity in the native milieu, suggesting that asymmetric occupancy of heteropentameric ion channels by alkylphenol-based anesthetics is sufficient to induce modulation of activity.</p>},
	keywords = {anesthesia, anesthetic, click chemistry, GABA receptor, photoaffinity labeling},
	doi = {10.1074/jbc.M116.736975},
	author = {Woll, Kellie A. and Murlidaran, Sruthi and Pinch, Benika J. and J{\'e}r{\^o}me H{\'e}nin and Wang, Xiaoshi and Salari, Reza and Covarrubias, Manuel and Dailey, William P. and Grace Brannigan and Garcia, Benjamin A. and Roderic G Eckenhoff}
}
