Molecular Dynamics Simulations of Biological Macromolecules

计算生物物理学研究部 利用几个理论探讨具有生物学意义的问题 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，以及分子图形。 这些技术被广泛应用于各种大分子 系统。应用于生物医学分子的特定项目 Interest使用分子动力学模拟来预测函数或 多肽和蛋白质的结构。这些计划包括： β-内酰胺类抗生素的反应机理模拟 大型复合病毒，人类犀牛病毒14(HRV14)-致死点 同源结构域/DNA复合体突变的研究 VND/NK-2基因A43T突变的模拟研究 HIV-1蛋白酶的作用机制--多肽的鉴定 与人MHC DR1结合的基础研究正在进行中 提供对大分子系统的更好理解。这个 项目包括：-模拟核酸和 NA/蛋白质复合体--模拟结构和蛋白质的依赖性 环境考虑的动力学--分子动力学 葡萄球菌核酸酶和其他蛋白质的模拟： 与核磁共振数据的比较--无偏强制抽样 复杂构象转变：a的传播 B-DNA/Z-DNA连接。-核酸的真实表示 在溶液中。C3a过敏性毒素的蛋白质-蛋白质对接研究 -醛糖还原酶催化机理的研究 QM/MM方法-DPPC脂双层的凝胶相模拟， 对比实验--《极限》的对比研究 嗜热性和相应的中嗜性蛋白质-DNA/蛋白质 相互作用：人类染色体的性别决定区域 -对锤头状核酶-底物复合系统进行建模- 利用分子动力学对亮氨酸拉链进行建模 β-内酰胺类抗生素，包括青霉素和 头孢菌素，受限于细菌的防御性活性 β-内酰胺酶。对反应机理进行了深入的研究。 但在实验上，它的特殊作用和质子化状态 所需的残留量仍不清楚。这部作品追溯了这两个 建议的反应机理使用混合量子和 经典治疗，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。 以降低催化率。

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.