DEVELOPING A NOVEL PHARMACOPHORE AND INVESTIGATING PROTEIN-PROTEIN INTERACTIONS

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 研究中心，而研究中心不一定是研究者所在的机构。 我的研究目标是研究相关生物酶的结构和功能，并进一步了解分子识别，包括蛋白质-配体和蛋白质-蛋白质相互作用。基础科学研究的结果正被用于开发新的药效团模型，这些模型解释了很大程度的受体灵活性，并在终点自由能模型以及更严格的计算方法方面理解和预测蛋白质-蛋白质缔合。这些目标将通过使用各种最先进的计算和理论方法来实现，包括：大规模并行传统和转向分子动力学，生物信息学，动态药效团模型和MM-PBSA。我的研究的两个重要目标是改进现有的技术，以及开发新的方法来解决这些问题。每个项目都确定了实验合作者，与知名领导人合作的机会将有助于确保研究的生物相关性和及时完成。

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. The goals of my research are to investigate the structure and function of relevant biological enzymes and to further the understanding of molecular recognition, both in terms of protein-ligand and protein-protein interactions. The results from the fundamental science investigations are being used to develop new pharmacophore models that account for a large degree of receptor flexibility, and to understand and predict protein-protein association, in terms of end-point free energy models, as well as more rigorous computational approaches. These goals will be accomplished through the use of a variety of state-of-the-art computational and theoretical methodologies, including: massively parallel traditional and steered molecular dynamics, bioinformatics, dynamic pharmacophore models, and MM-PBSA. Two important goals of my research are to improve already existing technologies, as well as to develop new methodologies in order to address these questions. Experimental collaborators have been identified within each project, and the opportunity to collaborate with established leaders will help ensure biological relevance and timely completion of the studies.