MULTIRESOLUTION SAMPLING METHODS FOR PROTEIN & PEPTIDE CONFORMATIONAL SPACE

在我们关于Long的核心研究项目的这个组成部分内 蛋白质和多肽折叠的时间尺度/长度尺度抽样 已经开发出蛋白质拓扑的“极简主义”表示法 基于简化的钙基相互作用模型的序列。这个 这些模型的开发已经自动化，使人们能够 构建这样一种蛋白质结构的表示并执行 在给出一个PDB文件的情况下，对该表示进行折叠研究。我们加入了 提供生产这些模型的自动化手段的过程 对于WWW上的科学家来说，因此允许广泛的科学家 社区调查其特定的折叠方面 蛋白质序列/拓扑。我们的协议产生CHARMM拓扑 和适用于热力学研究的参数文件和 这些模型的折叠动力学。我们用了这样的极简主义 模型与理论发展相结合，探索 蛋白质折叠的极简主义模型的“最优化”。我们的 研究表明，我们可以探索相当大范围的 使用这些方法的潜在能量函数空间，因此 显著降低开发的计算成本 蛋白质折叠的代表性极简主义模型。我们期待着 这些想法将被转移到DNA和RNA模型的研究中 以及涉及病毒组装的问题。我们在这方面的第一篇论文 这一主题最近已被接受发表在 化学物理学。完整的标题和参考资料是：探索 蛋白质折叠哈密顿空间：力的平衡 极简主义的b-Barrel模型。首页--期刊主要分类--期刊细介绍--期刊题录与期刊详细文摘内容 作者：C.L.Brooks III，J.物理，接受出版(1998)。 科学前沿1997-蛋白质折叠的化学物理。C。 首页--期刊主要分类--期刊细介绍--期刊题录与文摘--期刊详细内容 Press(1998)。

Within this component of our core research project on long timescale/length scale sampling for protein and peptide folding, we have developed "minimalist" representations of protein topologies and sequences based on simplified Ca-based interaction models. The development of these models has been automated allowing one to construct such a representation of a protein structure and carry out folding studies on this representation given a PDB file. We are in the process of providing an automated means of producing these models for scientists over the WWW, thus allowing scientists within the broad community to investigate the folding aspects of their particular protein sequences/topologies. Our protocol produces CHARMM topology and parameter files appropriate for studies of the thermodynamics and kinetics of folding of these models. We have used such minimalist models together with theoretical developments to explore the "optimization" of such minimalist models for protein folding. Our studies have demonstrated that we can explore a rather large range of the underlying energy function space using these methods and hence significantly reduce the computational cost of developing representative minimalist models for protein folding. We anticipate these ideas will be transferable to studies of DNA and RNA models as well as questions involving virus assembly. Our first paper on this topic has been recently accepted for publication in the Journal of Chemical Physics. The full title and references are: Exploring the Space of Protein Folding Hamiltonians: The Balance of Forces in a Minimalist b-Barrel Model. J.-E. Shea, Y. D. Nochomovitz, Z. Guo and C. L. Brooks III, J. Chem. Phys., accepted for publication (1998). Frontiers of Science 1997 - Chemical Physics of Protein Folding. C. L. Brooks III, M. Gruebele, J. N. Onuchic and P. G. Wolynes PNAS, in press (1998).