BioMaPS Institute for Quantitative Biology and Department of Chemistry and Chemical Biology, Rutgers University, Piscataway, NJ 08854, USA.
Curr Opin Struct Biol. 2011 Apr;21(2):161-6. doi: 10.1016/j.sbi.2011.01.010. Epub 2011 Feb 19.
Conformational dynamics plays a fundamental role in the regulation of molecular recognition processes. Conformational heterogeneity and entropy variations upon binding, although not always evident from the analysis of structural data, can substantially affect affinity and specificity. Computer modeling is able to provide some of the most direct insights into these aspects of molecular recognition. We review recent physics-based computational studies that employ advanced conformational sampling algorithms and effective potentials to model the three main classes of degrees of freedom relevant to the binding process: ligand positioning relative to the receptor, ligand and receptor internal reorganization, and hydration. Collectively these studies show that all of these elements are important for proper modeling of protein-ligand interactions.
构象动力学在分子识别过程的调控中起着至关重要的作用。尽管结合时的构象异质性和熵变并不总是从结构数据分析中明显看出，但它们可以极大地影响亲和力和特异性。计算机建模能够为分子识别的这些方面提供一些最直接的见解。我们综述了最近基于物理的计算研究，这些研究采用了先进的构象采样算法和有效势来模拟与结合过程相关的三个主要自由度类别：配体相对于受体的定位、配体和受体的内部重排以及水合作用。这些研究表明，所有这些因素对于正确模拟蛋白-配体相互作用都很重要。
