Empirical solvation models can be used to differentiate native from near-native conformations of bovine pancreatic trypsin inhibitor.
Empirical solvation models can be used to differentiate native from near-native conformations of bovine pancreatic trypsin inhibitor.
复制标题
经验溶剂化模型可用于区分牛胰蛋白酶抑制剂的天然构象和近天然构象。
DOI：
10.1002/prot.340100305
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发表时间：
1991
期刊：
影响因子：
2.9
通讯作者：
Scheraga,HA
中科院分区：
文献类型：
--
作者：
Vila,J;Williams,RL;Vasquez,M;Scheraga,HA
基于溶剂可及表面积的多肽和蛋白质水合模型已经被提出。我们已经评估了其中的一些模型，以及在蛋白质近天然构象的背景下的四个新模型。此外，我们提出了一个经验的网站-网站的距离依赖的校正，可用于与任何这些models.The集的近天然结构由39构象的牛胰胰蛋白酶抑制剂（BPTI），其中每一个是一个局部最小的经验能量函数（ECEPP）在没有溶剂的情况下。与晶体学测定结构的均方根（rms）偏差在以下范围内：对于所有重原子为1.06-1.94 nmol/L，对于所有主链重原子为0.77-1.36 nmol/L，对于所有α-碳原子为0.68-1.33 nmol/L，1.41- 2.72 μ m（所有侧链重原子）。我们发现，在一致性方面进行评估时，溶剂模型之间存在相当大的差异溶剂化自由能和结晶学确定的构象的RMS偏差之间的关系。由肽在水中的NMR偶合常数结合平均力势的指数位距依赖性导出的溶剂化模型与Cα原子的均方根偏差具有最好的一致性（0.939）.我们的结果表明，由非肽水合自由能导出的溶剂化自由能参数可能不适用于肽.由肽和蛋白质数据导出的参数可能更适用于蛋白质的构象分析。描述了从溶液中肽的系综平均性质导出水合自由能参数的一般方法。
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 conjuction 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 Å for all heavy atoms, 0.77–1.36 Å for all backbone heavy atoms, 0.68–1.33 Å for all α‐carbon atoms, and 1.41–2.72 Å 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 Cαatoms 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.