Chong L T, Dempster S E, Hendsch Z S, Lee L P, Tidor B
Department of Chemistry, Massachusetts Institute of Technology, Cambridge 02139-4307, USA.
Protein Sci. 1998 Jan;7(1):206-10. doi: 10.1002/pro.5560070122.
Recent evidence suggests that the net effect of electrostatics is generally to destabilize protein binding due to large desolvation penalties. A novel method for computing ligand-charge distributions that optimize the tradeoff between ligand desolvation penalty and favorable interactions with a binding site has been applied to a model for barnase. The result is a ligand-charge distribution with a favorable electrostatic contribution to binding due, in part, to ligand point charges whose direct interaction with the binding site is unfavorable, but which make strong intra-molecular interactions that are uncloaked on binding and thus act to lessen the ligand desolvation penalty.
最近的证据表明，由于巨大的去溶剂化惩罚，静电的净效应通常会使蛋白质结合不稳定。一种计算配体电荷分布的新方法已应用于巴那斯酶模型，该方法优化了配体去溶剂化惩罚与与结合位点的有利相互作用之间的权衡。结果是一种配体电荷分布，其对结合具有有利的静电贡献，部分原因是配体点电荷与结合位点的直接相互作用不利，但它们形成了强大的分子内相互作用，这些相互作用在结合时暴露出来，从而起到减轻配体去溶剂化惩罚的作用。
