项目名称: 基于序列和结构特征的人类蛋白酶底物裂解的生物信息学研究
项目编号: No.61202167
项目类型: 青年科学基金项目
立项/批准年度: 2013
项目学科: 计算机科学学科
项目作者: 宋江宁
作者单位: 中国科学院天津工业生物技术研究所
项目金额: 25万元
中文摘要: 由蛋白酶所调控的底物水解对于所有生命形式具有重要的基础意义。失控的蛋白酶底物水解则跟许多人类疾病密切相关,包括癌症、炎症以及心血管疾病等。蛋白酶对于所作用的反应底物有着严格的选择性,仅能特异性水解底物中特定位置的肽键。蛋白酶功能研究的核心瓶颈是如何准确识别所有的天然底物。掌握蛋白酶底物特异性知识能够极大提高我们预测酶底物以及设计抑制剂的能力,然而,目前这一信息获取只能依赖于实验手段。因而,本研究领域的一个核心问题是对底物特异性的准确预测能力相当有限。本课题以具有重要生物功能的几种人类半胱氨酸和丝氨酸蛋白酶为研究对象,旨在针对底物裂解位点临近序列和结构信息进行创新性、系统性的智能计算和生物信息分析及深入研究,找出决定底物特异性的重要序列和结构特征以及规律性信息,开发高效准确的蛋白酶底物裂解位点机器学习模型,为深入了解蛋白酶生化反应规律、底物识别和抑制剂设计提供重要信息与理论指导。
中文关键词: 蛋白酶;底物裂解特异性;生物信息算法;泛素化;蛋白质结晶
英文摘要: The ability of proteases to catalytically hydrolyse protein substrates with the removal of damaged or undesirable products is fundamental for all forms of life. The importance of protease-controlled proteolysis is apparent in numerous human pathological conditions related to alterations in proteases, including cancer, arthritis, inflammation, degenerative and cardiovascular diseases. Proteases act as processing enzymes that carry out either highly or moderately selective cleavage of the scissile bond after the specific cleavage site in their substrate. The key bottleneck to understanding the physiological role of a protease is to identify its natural substrate(s). Knowledge of the substrate specificity of a protease can dramatically improve our ability to predict target protein substrates and develop specific inhibitors; however, this information can at present only be derived from expensive and time-consuming experimental approaches. However, a major problem in the field is accurate prediction of the target specificity of proteases is currently not possible. In this project, we aim to develop bioinformatic approaches to make testable predictions in regards to the substrate specificity and biological targets of several cysteine and serine proteases, by focusing on the human cysteine and serine protease families,
英文关键词: protease;substrate cleavage specifity;Bioinformatics Algorithms;ubiquitination;protein crystallization