New energy terms for reduced protein models implemented in an off-lattice force field
New energy terms for reduced protein models implemented in an off-lattice force field
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DOI：
10.1002/jcc.1080
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发表时间：
2001-09-01
影响因子：
3
通讯作者：
Peräkylä, M
中科院分区：
文献类型：
--
作者：
Hassinen, T;Peräkylä, M
给出了一个含新能量项的约化蛋白质模型的参数化和检验计算。新的能量项以一种有效的方式保留了蛋白质侧链的空间特性和最重要的自由度，每个氨基酸残基仅使用一到三个虚拟原子。能量项在包含预定义的二级结构元素作为约束、静电相互作用项和溶剂可及表面积项以包括溶剂化效应的力场中实施。在力场中，主链肽单元被建模为电偶极子，其在α-螺旋和β-折叠中具有恒定的方向，而在环中具有可变的构象依赖性方向。蛋白质二级结构可以很容易地使用这些偶极子项建模。力场的参数是使用大量的实验蛋白质结构导出的，并通过最小化实验结构和使用分子动力学模拟生成的结构之间的RMS误差来进行细化。对于具有58-294个an-Lino酸残基的10种蛋白质的测试组，主链虚拟原子（C-α原子）的最终平均RMS误差为3.7埃，所有虚拟原子的最终平均RMS误差为4.2埃。用608种蛋白质的更大的测试集进一步测试力场，产生稍微较低的准确度。还使用一组27，814个错误折叠的诱饵结构来评估力场的折叠识别能力。(C)John Wiley & Sons，Inc.
Parameterization and test calculations of a reduced protein model with new energy terms are presented. The new energy terms retain the steric properties and the most significant degrees of freedom of protein side chains in an efficient way using only one to three virtual atoms per amino acid residue. The energy terms are implemented in a force field containing predefined secondary structure elements as constraints, electrostatic interaction terms, and a solvent-accessible surface area term to include the effect of solvation. In the force field the main-chain peptide units are modeled as electric dipoles, which have constant directions in alpha -helices and beta -sheets and variable conformation-dependent directions in loops. Protein secondary structures can be readily modeled using these dipole terms. Parameters of the force field were derived using a large set of experimental protein structures and refined by minimizing RMS errors between the experimental structures and structures generated using molecular dynamics simulations. The final average RMS error was 3.7 Angstrom for the main-chain virtual atoms (C-alpha atoms) and 4.2 Angstrom for all virtual atoms for a test set of 10 proteins with 58-294 an-Lino acid residues. The force field was further tested with a substantially larger test set of 608 proteins yielding somewhat lower accuracy. The fold recognition capabilities of the force field were also evaluated using a set of 27,814 misfolded decoy structures. (C) 2001 John Wiley & Sons, Inc.