REDUCED REPRESENTATION MODELS FOR PROTEIN FOLDING STUDIES: THERMODYNAMICS

蛋白质折叠研究的简化表示模型：热力学

• 批准号: 6283164
• 负责人: CHARLES L BROOKS
• 金额: $ 6.64万
• 依托单位: SCRIPPS RESEARCH INSTITUTE, THE
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-06-15 至 1999-06-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6283164
• 关键词: biological products; biomedical resource; computers; genetics; infection; informatics; structural biology; technology /technique

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).

在我们长期核心研究项目的这个组成部分中 蛋白质和肽折叠的时间尺度/长度尺度采样，我们 已经开发出蛋白质拓扑结构的“极简”表示， 序列的基础上简化的钙为基础的相互作用模型。 的 这些模型的开发已经自动化， 构建这样的蛋白质结构的表示，并执行 折叠的研究，这种表示给出了一个PDB文件。 我们在 提供自动化生产这些模型的方法 为科学家在万维网上，从而使科学家在广泛的 社区调查其特定的折叠方面， 蛋白质序列/拓扑结构。 我们的协议产生CHARMM拓扑 和参数文件，适用于热力学研究， 这些模型的折叠动力学。 我们使用了这种极简主义 模型和理论发展，以探讨 这种蛋白质折叠的极简模型的“优化”。 我们 研究表明，我们可以探索一个相当大的范围， 使用这些方法的基本能量函数空间，因此 显著降低开发的计算成本 蛋白质折叠的代表性极简模型。 我们预计 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。 我们的第一篇论文 该主题最近已被接受发表在杂志上， 化学物理 完整的标题和参考文献是：探索 蛋白质折叠哈密顿空间： 最低限度的b桶模型。 J. - E. Shea，Y. D. Nochomovitz，Z.郭和 C. L.布鲁克斯III，化学物理杂志，出版（1998年）。 科学前沿1997 -蛋白质折叠的化学物理。 C. L.布鲁克斯三世Gruebele，J. N. Onuchic和P.G. Wolynes PNAS，在 Press（1998）。