US-Turkey Cooperative Research: Peptide-Protein Docking and Binding Free Energy Calculation

0002127 Vajda描述：该奖项旨在支持马萨诸塞州波士顿市波士顿大学生物医学工程系Sandor Vajda博士和土耳其伊斯坦布尔图兹拉市萨班奇大学生物科学与生物工程系Ugur Sezerman博士的合作。 他们的目标是进一步开发和应用对接和结合自由能计算与蛋白质靶相互作用的线性分子，特别强调抗原肽和主要组织相容性复合体（MHC）蛋白之间的复合物形成。他们计划分三步努力：首先，通过将分子力学与经验溶剂化和熵项结合起来，开发自由能势。这些将被用作目标函数。 他们将获得的潜力将在一组蛋白质-肽对接诱饵上进行测试。 在第二步中，（经验证的）新电位将用作肽对接的靶函数。这将通过位点定位和片段组装对接方法进行。PI旨在通过利用动态编程实现片段对接计算的效率。 最后，他们计划应用这一程序，并在MHC I型和II型蛋白质上进行测试。这项研究将导致改进的柔性配体对接的计算机化方案。 这是一个需要解决的难题，以增加我们对蛋白质-蛋白质相互作用，药物开发和各种生物分子之间相互作用的理解。范围：该提案解决了分子建模中的一个重要问题：肽与蛋白质受体的对接和结合自由能的计算。 这个问题的结构和能量方面都很重要。预测配体-受体相互作用的结构方面和结合亲和力的能力对分子生物物理学以及新兴的结构生物信息学领域具有重要意义。主要研究者已经发表了一些关于这个和相关主题的论文，在目前的NSF资助下。 Sezerman教授曾与Vajda博士合作。这个项目将促进PI的团队和他在土耳其Sabanci大学的合作者团队之间的自然契合。 两地的专长和资源有很大的互补性。 该项目非常符合国际方案司鼓励在重要科学问题的研究方面进行互利合作的目标。

0002127VajdaDescription: This award is to support the collaboration of Dr. Sandor Vajda, Department of Biomedical Engineering, Boston University, Boston, Massachusetts and Dr. Ugur Sezerman, Department of Biological Sciences and Bioengineering, Sabanci University, Tuzla, Istanbul, Turkey. Their goal is to further develop and apply docking and binding free energy computations to linear molecules interacting with protein targets, with specific emphasis on complex formation between antigenic peptides and major histocompatibility complex (MHC) proteins. They plan a three-step effort: Initially, to develop free energy potentials, by essentially combining molecular mechanics with empirical solvation and entropic terms. These would be used as target functions. The potentials they would obtain are to be tested on a set of protein-peptide docked decoys. In the second step, the (validated) new potentials will be used as a target function for peptide docking. This will be performed both by site mapping and via fragment assembly docking methods. The PIs intend to achieve efficiency in the fragment-docking calculations through utilization of dynamic programming. Finally, they plan to apply this procedure and test it on the MHC type I and II proteins. The research should lead to improved computerized schemes of docking for flexible ligands. This is a difficult problem that needs solutions in order to increase our understanding of protein-protein interactions, drug development and interactions among various biological molecules.Scope: The proposal addresses an important problem in molecular modeling: docking of peptides to protein receptors and calculation of binding free energy. Both structural and energetic aspects of this problem are important. The ability to predict the structural aspects and the binding affinity of ligand-receptor interactions has important implications for molecular biophysics, as well as for the emerging area of structural bioinformatics. The principal investigator has published a number of papers on this and related topics, under current NSF funding. Prof. Sezerman has previously collaborated with Dr. Vajda. This project will promote a natural fit between the PI's group and the group of his collaborator at Sabanci University in Turkey. The areas of expertise and the resources in these two places are highly complementary. The project fits well with the objective of the Division of International Programs for encouraging mutually beneficial collaboration on research in important scientific problems.