Application of the PM6 method to modeling proteins
Application of the PM6 method to modeling proteins
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DOI：
10.1007/s00894-008-0420-y
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发表时间：
2009-07-01
影响因子：
2.2
通讯作者：
Stewart, James J. P.
中科院分区：
文献类型：
--
作者：
Stewart, James J. P.
研究了新发展的PM6方法对蛋白质建模的适用性。为了能够快速优化这类大系统的几何结构，对传统的半经验方法进行了三点改进：用定域分子轨道方法代替了求解自洽场方程的矩阵代数方法，用L-BFGS函数极小法代替了贝克几何优化的本征跟随方法，用点电荷和极化函数代替了NDDO近似集中的一些积分。所得到的方法被用于45种蛋白质的无约束几何优化，其大小从244个原子的简单九肽到14,566个原子的导入蛋白。对于大多数系统，PM6给出的结构与报道的X射线结构很好地一致。还计算了一些衍生性质，如pKa和体积弹性模数。通过模拟胰凝乳酶催化的多肽键的一个假想的反应步骤，研究了PM6在模拟过渡态方面的适用性。研究了一种从X射线结构开始产生精确蛋白质几何构型的拟议技术。
The applicability of the newly developed PM6 method for modeling proteins is investigated. In order to allow the geometries of such large systems to be optimized rapidly, three modifications were made to the conventional semiempirical procedure: the matrix algebra method for solving the self-consistent field (SCF) equations was replaced with a localized molecular orbital method (MOZYME), Baker's Eigenfollowing technique for geometry optimization was replaced with the L-BFGS function minimizer, and some of the integrals used in the NDDO set of approximations were replaced with point-charge and polarization functions. The resulting method was used in the unconstrained geometry optimization of 45 proteins ranging in size from a simple nonapeptide of 244 atoms to an importin consisting of 14,566 atoms. For most systems, PM6 gave structures in good agreement with the reported X-ray structures. Some derived properties, such as pKa and bulk elastic modulus, were also calculated. The applicability of PM6 to model transition states was investigated by simulating a hypothetical reaction step in the chymotrypsin-catalyzed hydrolysis of a peptide bond. A proposed technique for generating accurate protein geometries, starting with X-ray structures, was examined.