预测蛋白质相互作用位点的计算方法研究(一)

许多重要的细胞过程如信号转导、转运、细胞运动以及多数调节机制均由蛋白-蛋白之间的相可作用介导，蛋白质之间的相互作用在物理上是通过在两个相互作用蛋白之间形成接触面的短残基序列来实现。识别蛋白-蛋白相互作用位点，以及检测相互作用氨基酸残基之间的特异性与强度特异性，是一个具有重要应用前景的课题，它的应用范围从理性的药物设计到代谢和信号转导网络的分析。虽然有不少准确度不断提高的实验技术和计算方法来检测蛋白质之间的相互作用，但很少有方法能够精确地指出参与蛋白质相互作用的特定残基及其位置，而这些信息是将相互作用数据直接应用于药物开发所必需的。随着生物信息学和计算生物学的发展，通过研究已知蛋白-蛋白相互作用位点的这些不同特征．出现了一些利用序列与结构信息顶测蛋白-蛋白相互作用位点的计算方法。本文简要介绍了近年来在顶测蛋白-蛋白的相互作用位点方面取得一定进展的计算方法，包括基于基因组信息的计算方法、基于蛋白质初级序列的计算方法以及基于蛋白复合物结构信息的计算方法。虽然这些方法在过去儿年里取得了显著的进展，但是大多数在这方面的研究仍处于起步阶段．而现在数据库的不足和实验技术的缺陷对计算预测方法的进一步发展和公平性评价也存在着较大的影响，要提高蛋白-蛋白相巨作用位点预测的鲁棒性与可靠性，仍要有很多的工作要做。（发表在这里的是第一部分）

Research on Computational Methods of Prediction of Protein Interaction Sites

Many essential cellular processes such as mechanisms are mediated by protein-protein interactions. signal transduction,transport,cellular motion and most regulatory Physically,protein interactions are mediated by short sequences of residues that form the contact interfaces between two interacting proteins,often referred as their binding sites. Though many experimental methods and computational methods have been developed to detect protein interactions with increasing levels of accuracies, few methods can pinpoint the specific residues in the proteins that are involved in the interactions. Identification of protein-protein interaction sites and detection of specific amino acid residues that contribute to the specificity and strength of protein interactions is an important problem with applications ranging from rational drug design to analysis of metabolic and signal transduction networks. With the development of Bioinformatics and computational biology,some computational methods based on sequence and structure information by characterizing the known interaction sites for protein-protein interaction sites prediction is developed. We introduced several computational methods that have made some progress in protein-protein interaction sites prediction, including methods based on genomics, methods based on primary sequence and methods based on 3D structure information. With regard to these computational methods, combined approaches can reasonably accurately identify putative interacting sites, but these methods are, however, limited by the library of already solved structures and known interaction sites. Thus, while some progress has been made, the field is clearly in its infancy and much work will be required to bring the prediction of protein-protein interaction sites to a robust and reliable state.