A STUDY OF CORRELATED PROTEIN MOTIONS BY NORMAL MODE ANALYSES AND MOLECULAR DYN

正则模式分析和分子动力学对相关蛋白质运动的研究

• 批准号: 7723369
• 负责人: Lei Zhou
• 金额: $ 0.05万
• 依托单位: CARNEGIE-MELLON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-08-01 至 2009-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7723369
• 关键词: Computer Retrieval of Information on Scientific Projects Database; Funding; Grant; Hand; Institution; Methods; Molecular; Motion; Nature; Principal Component Analysis; Protein Conformation; Protein Dynamics; Proteins; Research; Research Personnel; Resolution; Resources; Roentgen Rays; Sampling; Solvents; Source; Structure; Surface; Time; United States National Institutes of Health; base; computer studies; molecular dynamics; network models

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. Correlated protein motions are of great functional significance and have been the target of various experimental and computational studies. Both molecular dynamics (MD) simulation and normal mode analysis (NMA) are able to provide information about the internal protein dynamics. Starting from a limited sampling of the protein conformation space, usually a section of MD simulation trajectory, principal component analysis (PCA, or essential dynamics) teases out the correlation motions through a diagonalization of the covariance matrix for the relevant atom group. The direction and amplitude of the vibrational modes are represented by the resulting eigenvectors and the corresponding eigenvalues, respectively. On the other hand, based on a harmonic assumption of the protein energy surface, normal mode analysis (NMA) yields the direction and amplitude of the correlated motion through diagonalization of the Hessian matrix, which contains the second derivative of the protein energy surface. Due to a limitation of computational resources, NMA approaches at different resolutions, from simplest elastic network model (ENM), block normal mode (BNM), to the classical all-atom normal mode methods, have been used more often than the time consuming MD-based PCA approach. However, the harmonic assumption of the energy surface and the implicit treatment of solvent make the NMA difficult to reproduce the often diffusive and anharmonic nature of protein dynamics. Here I propose to carry out parallel NMA and MD simulations on selected high resolution X-ray structures and comparing the results from both computational approaches to the experimentally determined parameters, including the isotropic vibrational amplitudes and anisotropic vibrational directionality. It is expected that MD-based PCA would bring a closer match to the experimental observations than does NMA.

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。 相关蛋白质运动具有重要的功能意义，并已成为各种实验和计算研究的目标。分子动力学（MD）模拟和简正模分析（NMA）都能够提供有关蛋白质内部动力学的信息。从蛋白质构象空间的有限采样开始，通常是MD模拟轨迹的一部分，主成分分析（PCA，或基本动力学）通过相关原子组的协方差矩阵的对角化来梳理相关运动。振动模式的方向和振幅分别由所得的本征向量和相应的本征值表示。另一方面，基于蛋白质能量表面的谐波假设，简正模分析（NMA）通过对角化包含蛋白质能量表面的二阶导数的Hessian矩阵来产生相关运动的方向和幅度。由于计算资源的限制，NMA方法在不同的分辨率，从最简单的弹性网络模型（ENM），块简正模（BNM），经典的全原子简正模方法，已被使用更多的时间比耗时的MD为基础的PCA方法。然而，能量表面的调和假设和溶剂的隐式处理使得NMA难以再现蛋白质动力学的经常扩散和非调和性质。在这里，我建议进行并行NMA和MD模拟选定的高分辨率X射线结构和比较的结果从两种计算方法的实验确定的参数，包括各向同性的振动振幅和各向异性的振动方向性。预计基于MD的PCA将比NMA更接近实验观察结果。