Molecular Dynamics Simulations of Biological Macromolecules

生物大分子的分子动力学模拟

• 批准号: 6109190
• 负责人: Bernard R Brooks
• 金额: --
• 依托单位: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6109190
• 关键词: chemical models; computer simulation; macromolecule; molecular dynamics; protein structure function; quantum chemistry

The Computational Biophysics Section studies problems of biological significance using several theoretical techniques: molecular dynamics, molecular mechanics, modeling, ab initio analysis of small molecule structure, and molecular graphics. These techniques are applied to a wide variety of macromolecular systems. Specific projects applied to molecules of biomedical interest uses molecular dynamics simulations to predict function or structures of peptides and proteins. Such projects include: - Reaction mechanisms of beta-lactam antibiotics - Simulation of a large virus complex, human rhino virus 14 (HRV14) - Lethal point mutations in homeodomain/DNA complexes: Investigation of the A43T mutation in vnd/NK-2 by simulation - Investigation of the mechanism of action of HIV-1 protease - Identification of peptides which bind to human MHC DR1 Basic research is underway to provide a better understanding of macromolecular systems. The projects include studies of: - Simulation of Nucleic Acids and NA/protein complexes - Dependence of simulated structure and dynamics on environmental considerations - Molecular dynamics simulations of staphylococcal nuclease and other proteins: comparison with NMR Data - Unbiased forced sampling of complex conformational transitions: Propagation of a B-DNA/Z-DNA junction. - Realistic representation of nucleic acids in solution. - Protein-protein Docking Study of C3a Anaphylatoxin - The study of the catalytic mechanism of aldose reductase using QM/MM methods - gel phase simulations of DPPC lipid bilayer, comparison with experiment - Comparison study of extreme thermophile and corresponding mesophile proteins - DNA/protein interactions: the sex-determining region of the human chromosome - Modeling the hammerhead ribozyme-substrate complex system - Modeling of leucine zippers using molecular dynamics The use of beta-lactam family of antibiotics, including penicillin and cephalosporin, is limited by the activity of the bacteria's defensive beta-lactamases. The reaction mechanism has been well studied experimentally but the specific role and protonation states of required residues are still unclear. This work traces the two suggested reaction mechanisms using a hybrid quantum and classical treatment in order to suggest the most probable path. Future work includes optimization of the beta-lactam substituents to reduce the rate of catalysis.

计算生物物理学研究 生物学意义的问题，使用几个理论 技术：分子动力学，分子力学，建模，ab 小分子结构的从头算分析和分子图形学。 这些技术适用于各种各样的大分子 系统.应用于生物医学分子的具体项目 兴趣使用分子动力学模拟来预测功能或 肽和蛋白质的结构。这些项目包括： β-内酰胺类抗生素的反应机理-模拟 大病毒复合物，人鼻病毒14（HRV 14）-致死点 同源结构域/DNA复合物中的突变： vnd/NK-2中A43 T突变的模拟研究 HIV-1蛋白酶的作用机制.肽的鉴定 与人MHC DR 1结合的基础研究正在进行中， 更好地理解大分子系统。的 项目包括：-模拟核酸和 NA/蛋白质复合物-依赖于模拟的结构和 环境动力学.分子动力学 葡萄球菌核酸酶和其他蛋白质的模拟： 与NMR数据的比较-无偏强制采样 复杂的构象转变： B-DNA/Z-DNA连接。- 核酸的现实表示 在溶液中。- 过敏毒素C3 a蛋白质-蛋白质对接研究 - 应用酶法研究醛糖还原酶的催化机理 QM/MM方法-DPPC脂质双层的凝胶相模拟， 与实验的比较--极端情况下的比较研究 嗜热菌和相应的嗜中温菌蛋白质- DNA/蛋白质 相互作用：人类染色体的性别决定区 - 模拟锤头状核酶-底物复合物系统- 亮氨酸拉链的分子动力学模拟 β-内酰胺类抗生素，包括青霉素和 头孢菌素，是有限的活动，细菌的防御 β-内酰胺酶。反应机理已得到很好的研究 实验上，但具体的作用和质子化状态的 所需的残留物仍不清楚。这项工作追溯了两者 建议的反应机制，使用混合量子和 经典的治疗，以建议最可能的路径。 未来的工作包括优化β-内酰胺取代基 以降低催化速率。