MOLECULAR DYNAMICS SIMULATIONS & METHOD DEVELOPMENT: DRUG DESIGN

我们使用计算机图形实验室的设施来显示和 分析分子动力学模拟结果。 我们的研究 项目的重点是a）改进、测试和开发新的 生成加性和非加性力场参数;以及B） 使用分子动力学进行大分子模拟。 新方法， 基于连续溶剂分析法， 分子动力学轨迹 这种新方法提供了直接 水溶液中溶质的自由能， 精度 我们已经应用这种方法来分析轨迹的 十二聚体双链体d（CGCGAATTCGCG）2及其氨基磷酸酯（N-P）类似物 在水溶液中。 连续溶剂定量分析 描述了正常DNA主要存在于B中的偏好 在水溶液中形成，而3'氨基磷酸酯修饰的DNA A型的双螺旋。 这项工作正在进一步发展， 加性和非加性琥珀力场 非加性琥珀 参数化包括基于原子的非加性效应 极化率和孤对相互作用。

We use the Computer Graphics Laboratory facilities to display and analyze the molecular dynamics simulations results. Our research projects focus on a) refining, testing and developing the new generation of additive and nonadditive force field parameters; and b) macromolecular simulation using molecular dynamics. The new approach, based on continuum solvent analysis, has been applied to analyze molecular dynamics trajectories. This new approach provides direct free energies of the solute in the aqueous solution with remarkable accuracy. We have applied this method to analyze trajectories of dodecamer duplex d(CGCGAATTCGCG)2 and its phosphoramidate (N-P) analog in water solution. The continuum solvent analysis quantitatively described the preference of the normal DNA to exist predominately in B form in water solution, whereas the 3' phosphoramidate modified DNA duplex in the A form. This work is undergoing further development of the additive and nonadditive AMBER force field. The nonadditive AMBER parametrization includes nonadditive effects based on atomic polarizabilities and lone pairs interactions.