Motifs for molecular recognition exploiting hydrophobic enclosure in protein-ligand binding. Export

@article{citeulike:1046671, abstract = {The thermodynamic properties and phase behavior of water in confined regions can vary significantly from that observed in the bulk. This is particularly true for systems in which the confinement is on the molecular-length scale. In this study, we use molecular dynamics simulations and a powerful solvent analysis technique based on inhomogenous solvation theory to investigate the properties of water molecules that solvate the confined regions of protein active sites. Our simulations and analysis indicate that the solvation of protein active sites that are characterized by hydrophobic enclosure and correlated hydrogen bonds induce atypical entropic and enthalpic penalties of hydration. These penalties apparently stabilize the protein-ligand complex with respect to the independently solvated ligand and protein, which leads to enhanced binding affinities. Our analysis elucidates several challenging cases, including the super affinity of the streptavidin-biotin system.}, author = {Young, Tom and Abel, Robert and Kim, Byungchan and Berne, Bruce J. and Friesner, Richard A.}, citeulike-article-id = {1046671}, citeulike-linkout-0 = {http://dx.doi.org/10.1073/pnas.0610202104}, citeulike-linkout-1 = {http://www.pnas.org/content/104/3/808.abstract}, citeulike-linkout-2 = {http://www.pnas.org/content/104/3/808.full.pdf}, citeulike-linkout-3 = {http://www.pnas.org/cgi/content/abstract/104/3/808}, citeulike-linkout-4 = {http://view.ncbi.nlm.nih.gov/pubmed/17204562}, citeulike-linkout-5 = {http://www.hubmed.org/display.cgi?uids=17204562}, day = {16}, doi = {10.1073/pnas.0610202104}, issn = {0027-8424}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, keywords = {docking, free\_energy, lipophilicity, sar, scoring, water\_replacement}, month = {January}, number = {3}, pages = {808--813}, posted-at = {2008-10-14 16:36:25}, priority = {2}, title = {Motifs for molecular recognition exploiting hydrophobic enclosure in protein-ligand binding.}, url = {http://dx.doi.org/10.1073/pnas.0610202104}, volume = {104}, year = {2007} }

TY - JOUR ID - citeulike:1046671 L3 - citeulike-article-id:1046671 N2 - The thermodynamic properties and phase behavior of water in confined regions can vary significantly from that observed in the bulk. This is particularly true for systems in which the confinement is on the molecular-length scale. In this study, we use molecular dynamics simulations and a powerful solvent analysis technique based on inhomogenous solvation theory to investigate the properties of water molecules that solvate the confined regions of protein active sites. Our simulations and analysis indicate that the solvation of protein active sites that are characterized by hydrophobic enclosure and correlated hydrogen bonds induce atypical entropic and enthalpic penalties of hydration. These penalties apparently stabilize the protein-ligand complex with respect to the independently solvated ligand and protein, which leads to enhanced binding affinities. Our analysis elucidates several challenging cases, including the super affinity of the streptavidin-biotin system. IS - 3 JF - Proceedings of the National Academy of Sciences of the United States of America SN - 0027-8424 EP - 813 TI - Motifs for molecular recognition exploiting hydrophobic enclosure in protein-ligand binding. VL - 104 SP - 808 KW - docking KW - free_energy KW - lipophilicity KW - sar KW - scoring KW - water_replacement AU - Young, Tom AU - Abel, Robert AU - Kim, Byungchan AU - Berne, Bruce AU - Friesner, Richard PY - 2007/01/16/ UR - http://dx.doi.org/10.1073/pnas.0610202104 ER -