THEORETICAL INVESTIGATIONS OF DNA POLYMERASES

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 在基础科学和应用科学领域，纳米技术和生物技术之间的界面正在迅速演变。在这个界面上，对潜在基本过程的定量描述本质上是一个多尺度的问题。在这个提议中，我们努力通过追求以下目标来实现与生物分子相互作用相关的平衡和动态过程的多尺度描述。(1)发展和应用自由能方法和量子力学分子力学(Qmmm)哈密顿量来描述酶的催化机理。(2)将自由能方法与分子动力学相结合来描述酶的构象活化和底物识别。(3)发展和应用多尺度空间分辨混合确定性/随机算法来研究信号转导。拟议的研究可能会在纳米生物技术和系统生物学方面产生重大影响，使基础科学发现成为可能，并推动合理的设计。

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.