The fragment molecular orbital method for geometry optimizations of polypeptides and proteins
The fragment molecular orbital method for geometry optimizations of polypeptides and proteins
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DOI：
10.1021/jp0671042
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发表时间：
2007-04-12
影响因子：
2.9
通讯作者：
Kitaura, Kazuo
中科院分区：
文献类型：
--
作者：
Fedorov, Dmitri G.;Ishida, Toyokazu;Kitaura, Kazuo
碎片分子轨道方法（FMO）已被用于大量的波函数的单点计算，其高精度的从头算方法相比，已被很好地建立。我们已经开发了远分离的片段之间的静电相互作用的解析导数，并进行了一些限制Hartree-Fock（RHF）的几何优化使用FMO和从头算方法。特别地，研究了10个残基聚丙氨酸的α-螺旋、β-转角和扩展构象，并建立了良好的FMO准确度（前两种形式的rms偏差约为0.2 A，后一种结构的rms偏差约为0.001 A）。甲硫氨酸-脑啡肽二聚体用作多肽结合的模型，并在3- 21 G和6- 31 G * 水平下计算，达到相似的准确度;结合能预测的误差（FMO vs ab initio）为1-3 kcal/mol。Chignolin（PDB：1uao）和促红细胞生成素受体蛋白的激动剂多肽（emp 1）在3-21（+）G水平上进行了优化，与从头算的rms偏差约为0.2 A，或键角为0.5度。通过用TIP 3 P描述水，研究了溶剂化对Chignolin和Trp-笼微蛋白构建体（PDB：112 y）中结构优化的影响。将计算得到的气相和溶液结构与实验结果进行了比较。
The fragment molecular orbital method (FMO) has been used with a large number of wave functions for single-point calculations, and its high accuracy in comparison to ab initio methods has been well established. We have developed the analytic derivative of the electrostatic interaction between far separated fragments and performed a number of restricted Hartree-Fock (RHF) geometry optimizations using FMO and ab initio methods. In particular, the alpha-helix, beta-turn, and extended conformers of a 10-residue polyalanine were studied and the good FMO accuracy was established (the rms deviations for the former two forms were about 0.2 A and for the latter structure about 0.001 A). Met-enkephalin dimer was used as a model for the polypeptide binding and computed at the 3-21G and 6-31G* levels with a similar accuracy achieved; the error in the binding energy predictions (FMO vs ab initio) was 1-3 kcal/mol. Chignolin (PDB: 1uao) and an agonist polypeptide of the erythropoietin receptor protein (emp1) were optimized at the 3-21(+)G level, with the rms deviation from ab initio of about 0.2 A, or 0.5 degrees in terms of bond angles. The effect of solvation on the structure optimization was studied in chignolin and the Trp-cage miniprotein construct (PDB:1l2y), by describing water with TIP3P. The computed structures in gas phase and solution are compared to each other and experiment.