Orientation-dependent potential of mean force for protein folding
Orientation-dependent potential of mean force for protein folding
复制标题
DOI：
10.1063/1.1940058
复制
发表时间：
2005-07-01
影响因子：
4.4
通讯作者：
Bagchi, B
中科院分区：
文献类型：
--
作者：
Mukherjee, A;Bhimalapuram, P;Bagchi, B
我们提出了一个溶剂隐式极简模型的蛋白质的氨基酸残基之间的潜力，通过使用已知的天然结构[存放在蛋白质数据库（PDB）]。在该模型中，氨基酸侧链由单个椭圆形位点表示，由侧链质心周围的原子团定义。这些椭圆形的网站与其他网站通过一个方向依赖的相互作用潜力，我们在以下方式构建。首先，计算了重原子间平均力的位-位势（PMF）[遵循F。梅洛和E. Feytsman，J. Mol. Biol.267，207（1997）]，从由晶体结构获得的它们的距离分离的统计数据。然后，这些位点-位点势用于计算所有氨基酸残基的侧链之间的距离和取向依赖性势（AAR）。距离和方向依赖性显示了几个有趣的结果。例如，我们发现，两个疏水阿尔斯之间的PMF，如苯丙氨酸，是强烈的吸引力在短距离（在非常短的分离明显的排斥区域后），其特征在于深最小值，为特定的方向。对于两个亲水性阿尔斯之间的相互作用，这样的深最小值是不存在的，此外，有趣的是，潜在的揭示了极性（电荷）和疏水相互作用的组合效果，其中一些阿尔斯。我们的潜力的有效性已经通过计算大量蛋白质的Z分数进行了测试。计算出的Z分数显示出高负值，其中大部分，标志着成功的潜力，以确定从大量的诱饵状态的天然结构。(c)2005年美国物理学会。
We present a solvent-implicit minimalistic model potential among the amino acid residues of proteins, obtained by using the known native structures [deposited in the Protein Data Bank (PDB)]. In this model, the amino acid side chains are represented by a single ellipsoidal site, defined by the group of atoms about the center of mass of the side chain. These ellipsoidal sites interact with other sites through an orientation-dependent interaction potential which we construct in the following fashion. First, the site-site potential of mean force (PMF) between heavy atoms is calculated [following F. Melo and E. Feytsman, J. Mol. Biol. 267, 207 (1997)] from statistics of their distance separation obtained from crystal structures. These site-site potentials are then used to calculate the distance and the orientation-dependent potential between side chains of all the amino acid residues (AAR). The distance and orientation dependencies show several interesting results. For example, we find that the PMF between two hydrophobic AARs, such as phenylalanine, is strongly attractive at short distances (after the obvious repulsive region at very short separation) and is characterized by a deep minimum, for specific orientations. For the interaction between two hydrophilic AARs, such a deep minimum is absent and in addition, the potential interestingly reveals the combined effect of polar (charge) and hydrophobic interactions among some of these AARs. The effectiveness of our potential has been tested by calculating the Z-scores for a large set of proteins. The calculated Z-scores show high negative values for most of them, signifying the success of the potential to identify the native structure from among a large number of its decoy states. (c) 2005 American Institute of Physics.