DEVELOPMENT AND APPLICATION OF A HIERARCHICAL PROTOCOL FOR AB INITIO PREDICTION

从头预测的分层协议的开发和应用

• 批准号: 7956074
• 负责人: HAROLD A. SCHERAGA
• 金额: $ 0.09万
• 依托单位: CARNEGIE-MELLON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-08-01 至 2010-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7956074
• 关键词: Amino Acids; Biological; Biomedical Research; Cereals; Charge; Code; Complex; Computational Biology; Computer Retrieval of Information on Scientific Projects Database; Development; Funding; Grant; High Performance Computing; Institution; Modeling; Molecular; Nucleic Acids; Physics; Process; Proteins; Protocols documentation; Research; Research Personnel; Resources; Route; Side; Signal Transduction; Simulate; Source; System; United States National Institutes of Health; base; improved; interest; molecular recognition; protein complex; simulation; three dimensional structure

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The interest in current computational biology is shifting from predicting the three-dimensional structure of proteins to simulating and understanding the mechanism of action of more complicated systems such as protein-protein, protein-nucleic acid complexes, and signal transduction processes. Research presented in this proposal is based on extension of our physics-based coarse-grained force-field UNRES. Three main extensions which we propose are: i) improved model for side chain-side chain interactions for better description of charge and polar interactions observed in proteins, which are important in molecular recognition and formation of protein-protein complexes; ii) introduction of the O-poshorylated residues into the UNRES model which will allow us to investigate molecular signaling routes; iii) massive parallelization of the code which will allow us to perform very fast MD simulations on systems composed of up to 1000 amino acids residues. We expect that all proposed changes will make our UNRES force-field more useful in understanding mechanism of action and function of large molecular systems that are important from a biological point of view.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 当前计算生物学的兴趣正在从预测蛋白质的三维结构转移到模拟和理解更复杂系统的作用机制，如蛋白质-蛋白质，蛋白质-核酸复合物和信号转导过程。在这项建议中提出的研究是基于我们的物理为基础的粗粒度力场UNRES的扩展。我们提出了三个主要的扩展：i）改进的侧链-侧链相互作用模型，以更好地描述蛋白质中的电荷和极性相互作用，这在分子识别和蛋白质-蛋白质复合物的形成中是重要的; ii）将O-磷酸化残基引入UNRES模型，使我们能够研究分子信号通路; iii）代码的大规模并行化，这将使我们能够在由多达1000个氨基酸残基组成的系统上进行非常快速的MD模拟。我们希望所有提出的变化将使我们的UNRES力场在理解从生物学角度来看重要的大分子系统的作用和功能机制方面更加有用。