Miyazawa S, Jernigan R L
Faculty of Technology Gunma Univrsity, Kiryu Gunma, Japan.
J Mol Biol. 1996 Mar 1;256(3):623-44. doi: 10.1006/jmbi.1996.0114.
Attractive inter-residue contact energies for proteins have been re-evaluated with the same assumptions and approximations used originally by us in 1985, but with a significantly larger set of protein crystal structures. An additional repulsive packing energy term, operative at higher densities to prevent overpacking, has also been estimated for all 20 amino acids as a function of the number of contacting residues, based on their observed distributions. The two terms of opposite sign are intended to be used together to provide an estimate of the overall energies of inter-residue interactions in simplified proteins without atomic details. To overcome the problem of how to utilize the many homologous proteins in the Protein Data Bank, a new scheme has been devised to assign different weights to each protein, based on similarities among amino acid sequences. A total of 1168 protein structures containing 1661 subunit sequences are actually used here. After the sequence weights have been applied, these correspond to an effective number of residue-residue contacts of 113,914, or about six times more than were used in the old analysis. Remarkably, the new attractive contact energies are nearly identical to the old ones, except for those with Leu and the rarer amino acids Trp and Met. The largest change found for Leu is surprising. The estimates of hydrophobicity from the contact energies for non-polar side-chains agree well with the experimental values. In an application of these contact energies, the sequences of 88 structurally distinct proteins in the Protein Data Bank are threaded at all possible positions without gaps into 189 different folds of proteins whose sequences differ from each other by at least 35% sequence identity. The native structures for 73 of 88 proteins, excluding 15 exceptional proteins such as membrane proteins, are all demonstrated to have the lowest alignment energies.
蛋白质中具有吸引力的残基间接触能已使用我们1985年最初使用的相同假设和近似方法进行了重新评估，但使用的蛋白质晶体结构集要大得多。还根据所有20种氨基酸的观察分布，估计了一个额外的排斥堆积能项，该项在更高密度下起作用以防止过度堆积，它是接触残基数量的函数。这两个符号相反的项旨在一起用于估计简化蛋白质中残基间相互作用的总能量，而无需原子细节。为了克服如何利用蛋白质数据库中众多同源蛋白质的问题，已设计出一种新方案，根据氨基酸序列之间的相似性为每种蛋白质赋予不同的权重。这里实际使用了总共1168个包含1661个亚基序列的蛋白质结构。应用序列权重后，这些对应于113,914个有效的残基 - 残基接触数，比旧分析中使用的接触数多大约六倍。值得注意的是，新的有吸引力的接触能与旧的几乎相同，除了那些涉及亮氨酸以及较罕见的氨基酸色氨酸和甲硫氨酸的接触能。亮氨酸的最大变化令人惊讶。从非极性侧链的接触能估计的疏水性与实验值吻合良好。在这些接触能的应用中，蛋白质数据库中88种结构不同的蛋白质序列在所有可能的位置无间隙地穿入189种不同的蛋白质折叠中，这些蛋白质折叠的序列彼此之间的序列同一性至少相差35％。88种蛋白质中的73种蛋白质的天然结构（不包括15种特殊蛋白质，如膜蛋白）都被证明具有最低的比对能。
