CONTINUUM ELECTROSTATISTICS THEORY

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。在研究蛋白质-配体相互作用时，人们往往侧重于分析蛋白质与配体原子/功能基团/残基之间的直接相互作用。然而，直接相互作用并不是决定结合亲和力价值的唯一因素。当配体与受体结合时，配体和受体的介电环境都会改变。介电环境的这种变化可以引入去溶惩罚，并改变蛋白质和配体中溶剂介导的分子内相互作用。例如，考虑蛋白质-配体界面附近的一个配体原子。它以前相对暴露在溶剂中，但结合后暴露较少。因此，在约束的情况下，会产生解体惩罚。此外，由于该原子的电荷在结合后由于结合口袋中的溶剂分子的位移而较少被溶剂屏蔽，因此它与其他原子的静电相互作用的强度由于有效介电常数的减小而增加，不仅是与蛋白质的原子，而且是与配体本身的原子。因此，在研究蛋白质与配体的结合时，重要的是要研究每个原子的溶剂化能的变化，以及除了蛋白质和配体之间的直接和溶剂介导的相互作用之外，配体和蛋白质内部的溶剂介导的分子内相互作用的变化。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. In studying protein-ligand interactions, one often focuses on analyzing the direct interactions between protein and ligand atoms/functional groups/residues. However, direct interactions are not the only factors that determine the value of a binding affinity. When a ligand binds to a receptor, the dielectric environments of both the ligand and the receptor are changed. This change in dielectric environments can introduce a desolvation penalty and alter the solvent-mediated intramolecular interactions in the protein and the ligand. For example, consider an atom of the ligand near the protein-ligand interface. It is relatively exposed to solvent before but is less exposed after binding. Therefore, a desolvation penalty results upon binding. Also, because the charge of this atom is less screened by the solvent after binding due to the displacement of solvent molecules in the binding pocket, the strength of its electrostatic interactions with other atoms, not only those with the proteins but also those within the ligand itself, is increased because of the diminished effective dielectric constant. Thus, in studying protein-ligand binding, it is important to examine the change in the solvation energy of each atom, and the change in the solvent-mediated intramolecular interactions within the ligand and within the protein in addition to the direct and solvent-mediated interactions between the protein and the ligand.