Protein sequence-structure alignments for predicting protein's structures and functions from their sequences

我们研究了以前开发的简单的潜在函数如何有效地识别序列和蛋白质结构之间的兼容性，用于数据库搜索。势函数由偶向接触能、过密排列残基的排斥性堆积势和二级结构的短程势组成，所有这些都是根据已知蛋白质结构中观察到的统计偏好估计的。每个势能项被修改以表示序列和结构之间的相容性。在序列-结构比对中的成对接触相互作用在待比对位点对概率的基础上用平均场近似来评估。假设间隙惩罚与每个残基位置的接触数成正比，因此在蛋白质表面上的间隙比在核心上的间隙更频繁。除了最小能量对齐外，我们还使用概率对齐，通过成对对齐概率依次对齐站点对。结果表明，所提出的能量函数和比对方法既能很好地检测与给定序列相容的序列，也能很好地检测与给定序列相容的序列，并且这两种类型的序列和结构对的比对结果基本相似。由最可靠的位点对组成的概率比对只能产生极小的均方根偏差，而包括较不可靠的位点对则会增加偏差。此外，我们还观察到，二级结构电位与用这种方法改进的产率相辅相成。值得注意的是，通过该方法检测到的个别序列结构对仅具有5- 20%的序列一致性。

We examine how effectively simple potential functions previously developed can identify compatibilities between sequences and structures of proteins for database searches. The potential function consists of pairwise contact energies, repulsive packing potentials of residues for overly dense arrangement and short-range potentials for secondary structures, all of which were estimated from statistical preferences observed in known protein structures. Each potential energy term was modified to represent compatibilities between sequences and structures for globular proteins. Pairwise contact interactions in a sequence-structure alignment are evaluated in a mean field approximation on the basis of probabilities of site pairs to be aligned. Gap penalties are assumed to be proportional to the number of contacts at each residue position, and as a result gaps will be more frequently placed on protein surfaces than in cores. In addition to minimum energy alignments, we use probability alignments made by successively aligning site pairs in order by pairwise alignment probabilities. Results show that the present energy function and alignment method can detect well both folds compatible with a given sequence and, inversely, sequences compatible with a given fold, and yield mostly similar alignments for these two types of sequence and structure pairs. Probability alignments consisting of most reliable site pairs only can yield extremely small root mean square deviations, and including less reliable pairs increases the deviations. Also it is observed that secondary structure potentials are usefully complementary to yield improved alignments with this method. Remarkably, by this method some individual sequence-structure pairs are detected having only 5-20 % sequence identity.