IMPROVING BIOMOLECULAR SIMULATIONS: ENERGY FUNCTIONS AND CONFORMATIONAL SAMPLIN

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。子项目及 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的研究机构。 我们建议继续我们的计算研究的折叠行为的几个模型多肽具有不同的二级结构基序和不同程度的拓扑复杂性。我们寻求深入了解蛋白质折叠的早期事件的性质，以及折叠和稳定性如何不仅与天然结构中的特定相互作用有关，而且与未折叠集合的组成有关。小，快速折叠系统已成为最近的蛋白质折叠研究的主题，我们的模拟将有助于提供详细的模型来解释实验观察。通过生成可由我们的合作者进行实验验证的假设来验证方法和参数是我们工作的一个关键方面。此外，我们建议继续进行DNA修复、结核病药物发现和蛋白质力场开发方面的其他几个项目。

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. We propose to continue our computational studies of the folding behavior of several model polypeptides with different secondary structure motifs and varying degrees of topological complexity. We seek insight into the nature of early events in protein folding and how folding and stability are related not only to specific interactions in the native structure but also to the composition of the unfolded ensemble. Small, fast-folding systems have become the subject of much recent research on protein folding, and our simulations will help provide detailed models for interpretation of experimental observations. Validation of methods and parameters via generation of hypotheses that are experimentally testable by our collaborators is a key aspect of our work. In addition, we propose to continue several other projects in DNA repair, tuberculosis drug discovery and protein force-field development.