Vila J, Williams R L, Vásquez M, Scheraga H A
Baker Laboratory of Chemistry, Cornell University, Ithaca, New York 14853-1301.
Proteins. 1991;10(3):199-218. doi: 10.1002/prot.340100305.
Several hydration models for peptides and proteins based on solvent accessible surface area have been proposed previously. We have evaluated some of these models as well as four new ones in the context of near-native conformations of a protein. In addition, we propose an empirical site-site distance-dependent correction that can be used in conjunction with any of these models. The set of near-native structures consisted of 39 conformations of bovine pancreatic trypsin inhibitor (BPTI) each of which was a local minimum of an empirical energy function (ECEPP) in the absence of solvent. Root-mean-square (rms) deviations from the crystallographically determined structure were in the following ranges: 1.06-1.94 A for all heavy atoms, 0.77-1.36 A for all backbone heavy atoms, 0.68-1.33 A for all alpha-carbon atoms, and 1.41-2.72 A for all side-chain heavy atoms. We have found that there is considerable variation among the solvent models when evaluated in terms of concordance between the solvation free energy and the rms deviations from the crystallographically determined conformation. The solvation model for which the best concordance (0.939) with the rms deviations of the C alpha atoms was found was derived from NMR coupling constants of peptides in water combined with an exponential site-site distance dependence of the potential of mean force. Our results indicate that solvation free energy parameters derived from nonpeptide free energies of hydration may not be transferrable to peptides. Parameters derived from peptide and protein data may be more applicable to conformational analysis of proteins. A general approach to derive parameters for free energy of hydration from ensemble-averaged properties of peptides in solution is described.
先前已提出了几种基于溶剂可及表面积的肽和蛋白质水合模型。我们在一种蛋白质的近天然构象背景下评估了其中一些模型以及四种新模型。此外,我们提出了一种经验性的位点 - 位点距离依赖性校正,可与这些模型中的任何一种结合使用。近天然结构集由牛胰蛋白酶抑制剂(BPTI)的39种构象组成,每种构象在无溶剂时都是经验能量函数(ECEPP)的局部最小值。与晶体学确定结构的均方根(rms)偏差在以下范围内:所有重原子为1.06 - 1.94 Å,所有主链重原子为0.77 - 1.36 Å,所有α - 碳原子为0.68 - 1.33 Å,所有侧链重原子为1.41 - 2.72 Å。我们发现,根据溶剂化自由能与晶体学确定构象的rms偏差之间的一致性来评估时,溶剂模型之间存在相当大的差异。与Cα原子的rms偏差一致性最佳(0.939)的溶剂化模型是从水中肽的NMR耦合常数以及平均力势的指数位点 - 位点距离依赖性推导出来的。我们的结果表明,从非肽水合自由能推导的溶剂化自由能参数可能无法转移到肽上。从肽和蛋白质数据推导的参数可能更适用于蛋白质的构象分析。描述了一种从溶液中肽的系综平均性质推导水合自由能参数的通用方法。