MODELING SECONDARY STRUCTURE ASSEMBLY IN PROTEIN CONFORMATIONAL SEARCH

蛋白质构象搜索中二级结构组装建模

• 批准号: 6280312
• 负责人: KAIZHI YUE
• 金额: $ 0.01万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-07-01 至 1999-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6280312
• 关键词: bioengineering /biomedical engineering; biological products; biomedical resource; biotechnology; computers; model design /development; technology /technique

I am currently involved in two research projects that deal with computational methods in the search for global minimum energy conformations in protein folding. The objective of the research is to properly define a simplified energy potential and find the conformations that have the minimum energy according to the potential such that the conformations with minimal energy are geometrically close to the known native structures. We have developed a thermodynamic model of protein folding that incorporates both hydrophobicity and polar interactions. The model uses a united atom representation, but with polar hydrogens explicitly represented. We found our current spatial representation was acceptable for working with small proteins. But for larger proteins with more complex topology, especially when packing of secondary structures is involved, our current representation will lead most of the search to steric conflicts, thus dead ends. As the focus of the first research project, I am now developing a representation that takes into the flexibility of the protein chain into account, dynamically adjust the phi/psi values of the chain yet maintain the uniform coverage of the conformational space in the search. Based on the preliminary results in the research on spatial representations, I am also currently developping algorithms for constructing hydrophobic cores of protein structures from given protein sequences. The second project is the continuing efforts to maintain and upgrade the program GEOCORE. After the publication of the paper on GEOCORE, I have added new functionalities and improved the user interface. These include the capability of searching for the geometrically best conformations in the vast conformational space defined by a given set of phi/psi choices.

我目前参与了两个研究项目， 寻找全局最小能量的计算方法 蛋白质折叠中的构象 研究的目的是 适当地定义一个简化的能量势， 根据势能，具有最小能量的构象 使得具有最小能量的构象在几何上 接近已知的天然结构。 我们已经开发出一种 蛋白质折叠的热力学模型， 疏水性和 极性相互作用 该模型使用统一的原子表示，但 其中明确表示了极性氢。 我们找到了 空间表示对于处理小蛋白是可接受的。 但是对于具有更复杂拓扑结构的较大蛋白质，特别是当 包装的二级结构涉及，我们目前的 代表性将导致大部分的搜索空间冲突，因此 死胡同 作为第一个研究项目的重点，我现在 开发一种表示法， 考虑到蛋白质链，动态调整phi/psi值， 链仍然保持构象的均匀覆盖， 空间在搜索 根据研究的初步结果， 在空间表示方面，我目前也在开发算法， 用于从给定的蛋白质结构构建疏水核心， 蛋白质序列 第二个项目是继续努力， 维护和升级GEOCORE程序。 发表后 在GEOCORE的论文中，我增加了新的功能，并改进了 用户界面。 其中包括搜索的能力， 在巨大的构象空间中的几何最佳构象 由给定的一组phi/psi选择来定义。