基于串线的3-维蛋白结构预测的新技术研究

项目名称： 基于串线的3-维蛋白结构预测的新技术研究

项目编号： No.60873207

项目类型： 面上项目

立项/批准年度： 2009

项目学科： 金属学与金属工艺

项目作者： 李国君

作者单位： 山东大学

项目金额： 35万元

中文摘要： 本项目计划研制一种新的基于串线技术的3-维蛋白结构预测的计算方案。传统的基于串线的蛋白结构计算技术只能利用碱基(residue)水平的信息，而忽略了原子（侧链）水平的信息。虽然在过去的十年里基于碱基水平的结构预测在计算方面取得了较大进步，但在预测精度方面给我们提出了新的挑战。为了跟上结构和功能基因组研究的快速发展，迫切需要新的更高精度的结构预测技术。为此，我们正在研究一种新的串线技术以充分利用原子水平的信息来提高预测精度，最终实现碱基和侧链同时地被准确定位。着重考虑如下几个方面：1、研究适合碱基和侧链同时定位的更有效的能量函数；2、研究新的计算策略以最小化上述能量函数，并实现碱基和侧链同时定位，即确定被测氨基酸序列和蛋白结构平台间的最优有序配对，以及每个碱基的侧链和平台可达构型位置间的最优定位；3、评估新的能量函数和算法来证实侧链在结构预测中的有威力；4、设计编辑软件，搭建网络服务平台。

中文关键词： 3-维蛋白结构预测；侧链；串线算法

英文摘要： We propose to develop a new paradigm for threading-based protein structure prediction. Traditionally, threading-based structure prediction uses only residue-level information,leaving out virtually all information about the side-chains of a protein. While such a residue-based approach has made it computationally feasible to predict structures for proteins of essentially any size in the past decade, we clearly see an urgent need now for more accurate prediction techniques that can provide higher resolution structural data, to meet the rapidly growing needs of structural and functional genomics studies. To address this challenging issue, we will develop a novel computational framework for solving a generalized threading problem, in which backbone threading and side-chain packing are predicted simultaneously. Specifically, we will (a) develop a new energy function that combines residue-level information for backbone threading and atom-level information for side-chain packing; (b) develop a novel algorithmic framework for solving the generalized threading problem, i.e., to find a sequence-structure alignment between a query and a template protein as well as an assignment of side-chain rotamers to individual residues of the query and the accessible structural positions in the template, that minimizes the energy function developed in (a); (c) extend this algorithmic framework to deal with more general threading problems such as constrained threading problems; (d) test and evaluate the new threading energy functions and algorithms to demonstrate the feasibility and the power of using side-chain information in protein structure prediction, and (e) develop a freely accessible web-based prediction server, based on the developments in (a) - (d).

英文关键词： 3D protein structure prodiction; Side chain; Threading;