MULTISCALE SIMULATIONS OF BIOMOLECULAR DYNAMICS

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。 生物分子结构的一种新兴观点是构象系综，其中一些决定了特定的功能。生物分子动力学决定了这些功能上重要的构象在生物分子生命过程中出现的频率，因此，调节其功能活性。蛋白质折叠、生物分子设计、细胞调控和生物技术等领域通常需要对分子构象有深入的了解。尽管最近在实验方法上取得了革命性的进展，但我们在对生物分子的结构和动力学方面进行采样和破译的能力方面仍然受到限制，这些生物分子对于维持细胞过程至关重要。因此，迫切需要新的和非常规的技术来揭示生物分子结构和相互作用的基本原理。我们自主开发的模拟引擎-离散分子动力学（DMD）在访问生物相关的时间和长度尺度方面至关重要。它比传统的分子动力学模拟快5到10个数量级。该建议的目标是利用网格计算环境中的多尺度模拟对生物分子动力学，稳定性和聚集的研究。我们创建了一个门户网站，名为iFold：http://ifold.dokhlab.org，为使用DMD探索蛋白质动力学提供了第一个在线门户。然而，需要大量的计算资源来支持iFold模拟。到目前为止，iFold后端使用的是基于Linux的本地集群资源。由于iFold的普遍吸引力，位于北卡罗来纳州的Renaissance Computing Institute（RENCI）已经扩大了他们对使iFold成为TeraGrid科学网关的支持。该提案旨在利用TeraGrid资源满足iFold的计算需求。

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. An emerging view of biomolecular structure is that of an ensemble of conformations, some of which determine specific functions. Biomolecular dynamics determines how often these functionally important conformations appear in the course of biomolecules life, and, therefore, modulates its functional activity. Areas, such as protein folding, biomolecular design, cell regulation, and biotechnology, often require deep understanding of molecular conformations. Despite recent revolutionary advances in experimental methodologies, we are still restrained in our ability to sample and decipher the structural and dynamic aspects of biomolecules that are critical for sustaining cellular processes. Thus, there is a crucial need for novel and unconventional techniques to uncover the fundamentals of biomolecular structure and interactions. Our indigenously developed simulation engine - discrete molecular dynamics (DMD) has been pivotal in accessing biologically relevant time and length scales. It is faster than traditional molecular dynamics simulations by 5 to 10 orders of magnitude. The goal of this proposal is to utilize multiscale simulations in a grid computing environment towards studies of biomolecular dynamics, stability and aggregation. We have created a web-portal, called iFold: http://ifold.dokhlab.org providing the first online gateway for exploring protein dynamics using DMD. However, extensive computational resources are needed to support iFold simulations. So far, a UNC based local cluster resource was used for iFold backend. Due to universal appeal of iFold, Renaissance Computing Institute (RENCI) at North Carolina has extended their support for making iFold a TeraGrid Science Gateway. This proposal aims at utilizing the TeraGrid resources towards computational needs of iFold.