Realistic protein folding with hydrophobic potentials

描述（由申请人提供） 这项研究是NIH资助#RO1-GM 52126的延伸，将主要在巴西巴西利亚大学与Antonio F.佩雷拉德阿劳霍。作为一个广泛的，长期的目标，它打算有助于在寻找一个势能函数适合realistric蛋白质模型的从头折叠模拟，这将可能从它们的氨基酸序列的蛋白质结构的预测。更具体地说，一个未指定的疏水性潜力，这已经研究了由外国合作者的小组在最低限度的晶格模型的背景下，将结合一个现实的，非晶格模型，与所有蛋白质重原子明确表示，这是开发并已在主要研究者的小组使用。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依赖于相对少量的参数，即每个单体或原子的疏水性，这取决于模型，因此，最终在氨基酸序列中编码的机会更大。然而，这少量的参数意味着，即使在晶格模型中，也很难为给定的原生结构找到合适的参数组合。由于非晶格模型的大的灵活性预计将大大加剧这个问题，序列独立，但物理动机的结构限制，主要是在骨架氢键的形式，将不得不被appropriate。该项目的主要直接目标是研究在多大程度上由非特异性疏水相互作用主导的潜力，这可以通过以前在晶格模型的背景下开发的方法获得，可以与物理动机的结构限制相结合，以折叠现实的，非晶格的蛋白质模型。

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.