Bahar I, Jernigan R L
Molecular Structure Section, National Cancer Institute, National Institutes of Health, Bethesda MD 20892-5677, USA.
J Mol Biol. 1997 Feb 14;266(1):195-214. doi: 10.1006/jmbi.1996.0758.
Residue-specific potentials between pairs of side-chains and pairs of side-chain-backbone interaction sites have been generated by collecting radial distribution data for 302 protein structures. Multiple atomic interactions have been utilized to enhance the specificity and smooth the distance-dependence of the potentials. The potentials are demonstrated to successfully discriminate correct sequences in inverse folding experiments. Many specific effects are observable in the non-bonded potentials; grouping of residue types is inappropriate, since each residue type manifests some unique behavior. Only a weak dependence is seen on protein size and composition. Effective contact potentials operating in three different environments (self, solvent-exposed and residue-exposed) and over any distance range are presented. The effective contact potentials obtained from the integration of radial distributions over the distance interval r < or = 6.4 A are in excellent agreement with published values. The hydrophobic interactions are verified to be dominantly strong in this range. Comparison of these with a newly derived set of effective contact potentials for closer inter-residue separations (r < or = 4.0 A) demonstrates drastic changes in the most favorable interactions. In the closer approach case, where the number of pairs with a given residue is approximately one, the highly specific interactions between charged and polar side-chains predominate. These closer approach values could be utilized to select successively the relative positions and directions of residue side-chains in protein simulations, following a hierarchical algorithm optimizing side-chain-side-chain interactions over the two successively closer distance ranges. The homogeneous contribution to stability is stronger than the specific contribution by about a factor of 5. Overall, the total non-bonded interaction energy calculated for individual proteins follows a dependence on the number of residues of the form of n1.28, indicating an enhanced stability for larger proteins.
通过收集302个蛋白质结构的径向分布数据，生成了侧链对之间以及侧链-主链相互作用位点对之间的残基特异性势能。利用了多种原子相互作用来提高势能的特异性并平滑其距离依赖性。在反向折叠实验中，这些势能被证明能够成功区分正确的序列。在非键合势能中可以观察到许多特定效应；对残基类型进行分组并不合适，因为每种残基类型都表现出一些独特的行为。仅观察到对蛋白质大小和组成的微弱依赖性。本文给出了在三种不同环境（自身、溶剂暴露和残基暴露）以及任何距离范围内起作用的有效接触势能。通过对距离区间r≤6.4 Å上的径向分布进行积分得到的有效接触势能与已发表的值非常吻合。验证了在该范围内疏水相互作用占主导且很强。将这些与一组新推导的、用于更近残基间距（r≤4.0 Å）的有效接触势能进行比较，结果表明最有利的相互作用发生了剧烈变化。在更近接近的情况下，即与给定残基配对的数量约为1时，带电和极性侧链之间的高度特异性相互作用占主导。遵循一种在两个连续更近的距离范围内优化侧链-侧链相互作用的分层算法，这些更近接近的值可用于在蛋白质模拟中依次选择残基侧链的相对位置和方向。对稳定性的均匀贡献比特异性贡献强约5倍。总体而言，为单个蛋白质计算的总非键合相互作用能对残基数的依赖形式为n1.28，表明较大蛋白质的稳定性增强。
