Realistic protein folding with hydrophobic potentials

具有疏水潜力的真实蛋白质折叠

• 批准号: 6844886
• 负责人: EUGENE I SHAKHNOVICH
• 金额: $ 3.38万
• 依托单位: HARVARD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-03-01 至 2007-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6844886
• 关键词: biochemical evolution; chemical kinetics; chemical models; computer program /software; computer simulation; hydropathy; protein folding; protein protein interaction; protein sequence; protein structure; thermodynamics

DESCRIPTION (provided by applicant) This research, an extension of NIH grant #RO1-GM52126, will be performed primarily in Brazil at the University of Brasilia in collaboration with Antonio F. Pereira de Araujo. As a broad, long-term objective, it intends to contribute in the search for a potential energy function appropriate for ab initio folding simulations of realistric protein models, which would possibilitate the prediction of protein structures from their amino acid sequences. More specifically, an unspecified hydrophobic potential, which has been studied by the foreign collaborator's group in the context of minimalist lattice models, will be combined with a realistic, off-lattice model, with all protein heavy atoms represented explicitly, which was developed and has been used in the principal investigator's group. The main advantage of the hydrophobic potential over more specific energy functions normally used is that it depends on a realtively small number of parameters, that is, the hydrophobicity of each monomer or atom, depending on the model, and, therefore, has a greater chance of being eventually encoded in the sequence of amino acids. This small number of parameters, however, implies that it is much harder, even in lattice models, to find the appropriate combination of parameters for a given native structure. Since the large flexibility of the off-lattice model is expected to aggravate this problem dramatically, sequence independent but physically motivated structural restrictions, mainly in the form of backbone hydrogen bonds, will have to be appied. The main immediate goal of the project is then to investigate to what extent a potential dominated by unspecific hydrophobic interactions, which can be obtained by the approach previously developed in the context of lattice models, can be combined with physically motivated structural restrictions to fold realistic, off-lattice, protein models.

描述（由申请人提供） 这项研究是 NIH 拨款 #RO1-GM52126 的延伸，将主要在巴西巴西利亚大学与 Antonio F. Pereira de Araujo 合作进行。作为一个广泛的长期目标，它打算致力于寻找适合现实蛋白质模型从头开始折叠模拟的势能函数，这将有可能根据氨基酸序列预测蛋白质结构。更具体地说，外国合作者小组在极简晶格模型的背景下研究了未指定的疏水势，该模型将与现实的非晶格模型相结合，明确表示所有蛋白质重原子，该模型是由主要研究人员小组开发并使用的。与通常使用的更具体的能量函数相比，疏水势的主要优点是它取决于相对较少的参数，即每个单体或原子的疏水性，具体取决于模型，因此最终被编码在氨基酸序列中的机会更大。然而，如此少量的参数意味着即使在晶格模型中，为给定的本机结构找到适当的参数组合也更加困难。由于离格模型的巨大灵活性预计会极大地加剧这个问题，因此必须应用与序列无关但物理驱动的结构限制，主要以主链氢键的形式。该项目的主要直接目标是研究由非特异性疏水相互作用主导的势能在多大程度上可以通过先前在晶格模型背景下开发的方法获得，与物理驱动的结构限制相结合以折叠现实的、非晶格的蛋白质模型。