MOLECULAR FLEXIBILITY IN DRUG DESIGN USING MICROSECOND MOLECULAR DYNAMICS

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 McCammon小组的研究重点是生物分子复合物的分子动力学（MD）模拟，特别强调与被忽视疾病相关的药物发现。在这项提案中，我们描述了三个项目，旨在了解大规模的蛋白质运动和推进药物发现，包括受体的灵活性和蛋白质和脂质膜动力学的准确描述。在其中两个项目中，我们将通过使用基于微秒模拟轨迹后处理的有前途的单步扰动型方法来进行方法学开发。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The research of the McCammon group focuses on Molecular dynamics (MD) simulations of biomolecular complexes, with a particular emphasis on drug discovery related to neglected diseases. In this proposal we describe three projects aimed at understanding large-scale protein motions and advancing drug-discovery by including receptor flexibility and an accurate description of protein and lipid membrane dynamics. In two of these projects, we will pursue as well methodological development through the use of promising One-Step Perturbation type approaches based on post-processing of such microsecond simulation trajectories.