Molecular Recognition and Ligand Association

被引:156
作者
Baron, Riccardo [1 ,2 ]
McCammon, J. Andrew [3 ,4 ]
机构
[1] Univ Utah, Coll Pharm, Dept Med Chem, Salt Lake City, UT 84112 USA
[2] Univ Utah, Henry Eyring Ctr Theoret Chem, Salt Lake City, UT 84112 USA
[3] Univ Calif San Diego, Howard Hughes Med Inst, Dept Chem & Biochem, Dept Pharmacol, La Jolla, CA 92093 USA
[4] Univ Calif San Diego, Ctr Theoret Biol Phys, La Jolla, CA 92093 USA
来源
ANNUAL REVIEW OF PHYSICAL CHEMISTRY, VOL 64 | 2013年 / 64卷
基金
美国国家科学基金会;
关键词
thermodynamics; molecular simulation; configurational ensemble; solvent; wetting transitions; FREE-ENERGY CALCULATIONS; BINDING FREE-ENERGIES; SOLVATION FREE-ENERGIES; CONFORMATIONAL SELECTION; CONFIGURATIONAL ENTROPY; THERMODYNAMIC-INTEGRATION; COMPUTATIONAL ANALYSIS; STATISTICAL-MECHANICS; DEWETTING TRANSITIONS; EFFICIENT CALCULATION;
D O I
10.1146/annurev-physchem-040412-110047
中图分类号
O64 [物理化学(理论化学)、化学物理学];
学科分类号
070304 ; 081704 ;
摘要
We review recent developments in our understanding of molecular recognition and ligand association, focusing on two major viewpoints: (a) studies that highlight new physical insight into the molecular recognition process and the driving forces determining thermodynamic signatures of binding and (b) recent methodological advances in applications to protein-ligand binding. In particular, we highlight the challenges posed by compensating enthalpic and entropic terms, competing solute and solvent contributions, and the relevance of complex configurational ensembles comprising multiple protein, ligand, and solvent intermediate states. As more complete physics is taken into account, computational approaches increase their ability to complement experimental measurements, by providing a microscopic, dynamic view of ensemble-averaged experimental observables. Physics-based approaches are increasingly expanding their power in pharmacology applications.
引用
收藏
页码:151 / 175
页数:25
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