DEVELOPMENT AND APPLICATION OF A HIERARCHICAL PROTOCOL FOR AB INITIO PREDICTION

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 目前对计算生物学的兴趣正在从预测蛋白质的三维结构转向模拟和理解更复杂的系统的作用机制，如蛋白质-蛋白质、蛋白质-核酸复合体和信号转导过程。本提案中提出的研究是基于我们的基于物理的粗粒度力场UNRES的扩展。我们提出的三个主要扩展是：i)改进的侧链-侧链相互作用模型，更好地描述了蛋白质中观察到的电荷和极性相互作用，这在分子识别和蛋白质-蛋白质复合体的形成中是重要的；ii)将O-短链残基引入UNRES模型，这将使我们能够研究分子信号途径；iii)代码的大规模并行化，使我们能够对由多达1000个氨基酸残基组成的系统进行非常快速的MD模拟。我们期望所有拟议的改变将使我们的UNRES力场更有助于理解从生物学角度而言重要的大分子系统的作用机制和功能。

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.