Fang Qiaojun, Shortle David
Department of Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Proteins. 2005 Jul 1;60(1):97-102. doi: 10.1002/prot.20483.
In the preceding article in this issue of Proteins, an empirical energy function consisting of 4 statistical potentials that quantify local side-chain-backbone and side-chain-side-chain interactions has been demonstrated to successfully identify the native conformations of short sequence fragments and the native structure within large sets of high-quality decoys. Because this energy function consists entirely of interactions between residues separated by fewer than 5 positions, it can be used at the earliest stage of ab initio structure prediction to enhance the efficiency of conformational search. In this article, protein fragments are generated de novo by recombining very short segments of protein structures (2, 4, or 6 residues), either selected at random or optimized with respect this local energy function. When local energy is optimized in selected fragments, more efficient sampling of conformational space near the native conformation is consistently observed for 450 randomly selected single turn fragments, with turn lengths varying from 3 to 12 residues and all 4 combinations of flanking secondary structure. These results further demonstrate the energetic significance of local interactions in protein conformations. When used in combination with longer range energy functions, application of these potentials should lead to more accurate prediction of protein structure.
在本期《蛋白质》的上一篇文章中，一种由4种统计势组成的经验能量函数已被证明能够成功识别短序列片段的天然构象以及大量高质量诱饵结构中的天然结构，这4种统计势用于量化局部侧链-主链和侧链-侧链相互作用。由于该能量函数完全由相隔少于5个位置的残基之间的相互作用组成，因此它可用于从头预测结构的最早阶段，以提高构象搜索的效率。在本文中，通过重组蛋白质结构的非常短的片段（2、4或6个残基）从头生成蛋白质片段，这些片段要么是随机选择的，要么是根据这种局部能量函数进行优化的。当在选定片段中优化局部能量时，对于450个随机选择的单圈片段，始终观察到在天然构象附近的构象空间有更有效的采样，这些片段的圈长从3到12个残基不等，且侧翼二级结构有所有4种组合。这些结果进一步证明了局部相互作用在蛋白质构象中的能量学意义。当与更远程的能量函数结合使用时，应用这些势应该能够更准确地预测蛋白质结构。
