Simulating Protein Structures, Complexes, And Dynamics

模拟蛋白质结构、复合物和动力学

• 批准号: 6675525
• 负责人: PETER J STEINBACH
• 金额: --
• 依托单位: CENTER FOR INFORMATION TECHNOLOGY
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6675525
• 关键词: active sites; acyltransferase; aldehyde reductase; calcium channel; carboxypeptidase; chemical binding; chemical kinetics; chemical models; computer simulation; crystallins; dihydrofolate reductase; enzyme structure; isomerase; molecular dynamics; protein structure function; quantum chemistry; structural biology

Our investigation of the structure and function of carboxypeptidase E was published, and our study of the dynamics of loop formation in disordered peptides is in press. The design of a stable four-helix bundle protein using several experimental and modeling techniques is also in press. We are preparing a manuscript characterizing antibiotic binding to dihydrofolate reductase. We continue to refine our model of the human calcium receptor. Two papers on the catalytic mechanism of chorismate mutase studied using the combined potentials of quantum mechanics and molecular mechanics are in press. A manuscript on the mechanism of N-actyltransferase is in progress. A paper that describes the simulation of molecular dynamics to investigate the hydrogen bonding interactions between aldose reductase and its inhibitor tolrestat has been accepted for publication. Quantum chemical calculations are being carried out to invesigate the binding mode of the anti-cancer agent geldanamycin to hsp90. Quantum chemical calculations are also being carried out to quantify the interaction energy between propanediol and water molecules. Molecular modeling studies on the A-beta amyloid probes are also being carried out to establish a structure-activity relationship. A hybrid algorithm combining the maximum entropy method and nonlinear least-squares fitting was developed to analyze kinetics data. Fluorescence studies of protein folding were analyzed. The computer program, called MemExp, is available online. A paper describing this work was published, and a follow-up extension to the software is in press.

我们对羧基肽酶E的结构和功能的研究已经发表，我们对无序多肽中环形成的动力学的研究正在进行中。使用几种实验和建模技术设计稳定的四螺旋集束蛋白也在进行中。 我们正在准备一份手稿，描述抗生素与二氢叶酸还原酶的结合。我们继续完善我们的人类钙受体模型。 利用量子力学和分子力学的结合势研究分支酸变位酶的催化机理的两篇论文正在出版中。关于N-乙酰基转移酶机制的手稿正在进行中。 一篇描述分子动力学模拟研究醛糖还原酶及其抑制剂托瑞司他之间氢键相互作用的论文已被接受发表。 目前正在进行量子化学计算，以研究抗癌药物格尔达霉素与HSP90的结合模式。还在进行量子化学计算，以量化丙二醇和水分子之间的相互作用能。对A-β淀粉样蛋白探针的分子模拟研究也在进行中，以建立结构-活性关系。 一种最大熵法与非线性相结合的混合算法 采用最小二乘拟合法对动力学数据进行分析。对蛋白质折叠的荧光研究进行了分析。这款名为MemExp的电脑程序可以在网上下载。一篇描述这项工作的论文已经发表，该软件的后续扩展正在出版中。