Biomolecular Interactions and Enzymatic Processes

项目主任/首席调查员(末位、第一位、中位)：高，佳丽 项目摘要 一个多方面的研究项目针对的是光化学诱导的计算研究 光感受器蛋白质中的过程和相互作用。理论方法以分子动力学为中心。 超快激发能量转移和电荷转移的非绝热量子动力学模拟 以及随后触发信号转导的蛋白质构象变化。我们采用多尺度 模拟技术，包括量子力学和分子力学(QM/MM)相结合的方法 来描述分子间的相互作用。一个主要的目标是提高QM/MM方法的建模能力 该方法可用于光化学过程，并实现比传统方法更高的精度。我们建议 发展多态密度泛函理论(MSDFT)来定义激发态、电荷态和自旋局域态。 我们还计划进一步探索计算高效的多态紧束缚密度泛函理论 (MS-DFTB)执行长时间动态仿真。MSDFT方法遵循先动态后静态的 ANSATZ，其中动态关联首先被并入基态。因此，基础是 活动空间中的配置高度精简，这显著减少了 所需配置和计算成本。然而，MSDFT也是准确的。应用 MSDFT/CHARMM相结合，我们旨在了解光化学和光物理的本质 在隐色素光吸收之后的过程。此外，我们的目标是了解光收集 UV-B受体UVR8的机制及其光诱导二聚体光解离过程。一个很长的- 术语目标是了解UVR8和同源蛋白质之间蛋白质-蛋白质相互作用的性质。 PHS 398/2590(06/09版)页面续格式页面

Program Director/Principal Investigator (Last, First, Middle): Gao, Jiali Project Summary A multi-faceted research project is directed aimed at computational studies of photochemically induced processes and interactions in photoreceptor proteins. The theoretical approach centers on molecular dynamics and nonadiabatic quantum dynamics simulations of the ultrafast excited energy transfer and charge transfer as well as the subsequent protein conformation change that triggers signal transduction. We employ multiscale simulation techniques, including combined quantum mechanical and molecular mechanical (QM/MM) methods to describe intermolecular interactions. A major goal is to increase the capability of QM/MM methods to model photochemical processes and to achieve greater accuracy than conventional approaches. We propose to develop multistate density functional theory (MSDFT) to define excitation, charge, and spin localized states. We also plan on further explore the computationally efficient multistate tight-binding density functional theory (MS-DFTB) to perform long-time dynamics simulations. The MSDFT method follows a dynamic-then-static ansatz, in which dynamic correlation is incorporated into the basis states in the first place. As such, the basis configurations in the active space are highly contracted, which significantly reduce the number of configurations needed and the computational costs. Yet, MSDFT is also accurate. Applying the MSDFT/CHARMM combination, we aim to understand the nature of the photochemical and photophysical processes following light absorption in cryptochromes. In addition, we aim to understand the light harvesting mechanism of the ultraviolet-B receptor UVR8, and its light-induced dimer photodissociation process. A long- term goal is to understand the nature of protein-protein interactions between UVR8 and homologous proteins. PHS 398/2590 (Rev. 06/09) Page Continuation Format Page