THEORETICAL INVESTIGATIONS OF DNA POLYMERASES

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 中心，但不一定是研究者所在的机构。 在基础科学和应用科学领域，纳米技术和生物技术之间的接口正在迅速发展。在这个界面上，基本过程的定量描述本质上是一个多尺度问题。在这个建议中，我们努力实现多尺度描述的平衡和动态过程相关的生物分子相互作用，追求以下目标。(1)开发和应用自由能方法结合量子力学分子力学（QMMM）哈密尔顿描述酶催化机制。(2)应用自由能方法结合分子动力学描述酶的构象激活和底物识别。(3)开发和应用多尺度空间分辨混合确定性/随机算法研究信号转导。拟议中的研究可能会对纳米生物技术和系统生物学产生重大影响，从而实现基础科学发现，并推动合理设计。

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. In the realm of fundamental and applied sciences, the interface between nanotechnology and biotechnology is rapidly evolving. At this interface, quantitative description of underlying fundamental processes is inherently a multiscale problem. In this proposal, we strive to achieve a multiscale description of equilibrium and dynamic processes associated biomolecular interactions by pursuing the following aims. (1) Develop and apply free energy methods in conjunction with a quantum mechanics molecular mechanics (QMMM) Hamiltonian to describe enzyme catalytic mechanisms. (2) Apply free energy methods in conjunction with molecular dynamics to descrive enzyme conformational activation and substrate recognition. (3) Develop and apply multiscale spatially resolved hybrid deterministic/ stochastic algorithms for studying signal transduction. The proposed studies are likely to have a significant impact in nanobiotechnology and systems biology in terms of enabling fundamental scientific discoveries, as well as driving rational design.