THEORETICAL STUDIES OF PROTEIN FOLDING

蛋白质折叠的理论研究

• 批准号: 6127490
• 负责人: RICHARD A FRIESNER
• 金额: $ 18.05万
• 依托单位: COLUMBIA UNIV NEW YORK MORNINGSIDE
• 依托单位国家: 美国
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-01-01 至 2004-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6127490
• 关键词: chemical kinetics; chemical models; computer simulation; mathematical model; method development; model design /development; nuclear magnetic resonance spectroscopy; protein folding; protein sequence; quantum chemistry; thermodynamics

This proposal describes new methods for protein secondary structure prediction, tertiary folding to low resolution using reduced protein models, and structural refinement using atomic level potential functions and a continuum model for the solvation free energy. The methods will be applied to ab initio prediction of protein structure, threading, loop refinement in homology modeling, and protein structure determination from sparse NMR datasets. Specific methodological areas of focus include: (1) new scoring functions for secondary structure prediction; (2) development of a reduced potential function, and global optimization methods for tertiary folding; (3) construction of a polarizable protein potential function using ab initio quantum chemical data; (4) improvement of Poisson-Boltzmann and generalized Born continuum solvation models; (5) inclusion of NMR constraints in the tertiary folding methodology.

该提案描述了蛋白质二级结构预测、使用简化蛋白质模型进行三级折叠至低分辨率以及使用原子水平势函数和溶剂化自由能连续模型进行结构细化的新方法。 该方法将被应用于从头预测蛋白质结构，线程，环的同源性建模，并从稀疏的NMR数据集的蛋白质结构的确定细化。 具体的方法学领域包括：（1）二级结构预测的新评分函数;（2）三级折叠的约化势函数和全局优化方法的发展;（3）使用从头算量子化学数据构建可极化蛋白质势函数;（4）Poisson-Boltzmann和广义Born连续溶剂化模型的改进;（5）在三级折叠方法中加入NMR限制。