von Freyberg B, Richmond T J, Braun W
Institut für Molekularbiologie und Biophysik, ETH Hönggerberg, Zürich, Switzerland.
J Mol Biol. 1993 Sep 20;233(2):275-92. doi: 10.1006/jmbi.1993.1506.
With the program FANTOM, we study the effect of a solvation energy term modelled by four atomic solvation parameter sets on energy refinement of proteins. Two parameter sets had previously been derived from measured free energies of transfer of hydrocarbons and amino acid side-chain analogues. Alternatively, the other two parameter sets correspond to the total or apolar accessible surface area of the protein. Twenty-five conformations of BPTI and the alpha-amylase inhibitor tendamistat were refined with respect to empirical energy terms (ECEPP/2) plus a solvation energy term modelled by one of the four atomic solvation parameter sets. These minimizations were compared to minimizations of the ECEPP/2 energy alone with regard to violations of upper distance limits obtained from NMR experiments as well as to root mean square deviations to NMR structures. We find that minimizations of the ECEPP/2 energy plus the total or apolar accessible surface area are superior to minimizations of the ECEPP/2 energy alone. In contrast, minimization of the ECEPP/2 energy plus a solvation energy term based on free energies of transfer perform poorly.
通过FANTOM程序，我们研究了由四个原子溶剂化参数集建模的溶剂化能项对蛋白质能量优化的影响。其中两个参数集先前是从测量的碳氢化合物和氨基酸侧链类似物的转移自由能推导而来的。另外，其他两个参数集对应于蛋白质的总可及表面积或非极性可及表面积。针对经验能量项（ECEPP/2）加上由四个原子溶剂化参数集中的一个建模的溶剂化能项，对BPTI和α-淀粉酶抑制剂tendamistat的25种构象进行了优化。将这些最小化结果与仅对ECEPP/2能量进行最小化的结果进行了比较，比较内容包括违反从NMR实验获得的距离上限的情况以及与NMR结构的均方根偏差。我们发现，ECEPP/2能量加上总可及表面积或非极性可及表面积的最小化优于仅对ECEPP/2能量进行的最小化。相比之下，基于转移自由能的ECEPP/2能量加上溶剂化能项的最小化效果较差。
