COMPUTER SIMULATION METHOD FOR CALCULATING FREE ENERGY

计算自由能的计算机模拟方法

• 批准号: 3498602
• 负责人: RICHARD Masten FINE
• 金额: $ 5万
• 依托单位: BIOSYM TECHNOLOGIES, INC.
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-01-15 至 1991-07-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3498602
• 关键词: biophysics; chemical models; chemical stability; computer simulation; conformation; gonadotropin releasing factor; mathematical model; molecular dynamics; peptide structure; protein folding; protein structure; synthetic peptide; thermodynamics

The biological activity of polypeptides and proteins is determined, to a large extent, by their spatial structure. Therefore, calculation of the free energy F is important since minimum F is the criterion for conformational stability. However, with the usual simulation techniques calculation of F is difficult. The "local states method" suggested by Meirovitch is a procedure which enables one to extract F from computer simulation samples; it is independent of other techniques (such as thermodynamic integration methods) and has the following advantages: 1) The method can be applied to any chain flexibility, stable states as well the random coil or states which are mixtures of these two extreme cases, and 2) It can be used to obtain deltaF between two states with a large structural difference. The local states method has been successfully applied to lattice models and to a realistic continuum model of decaglycine. Our short term goal (Phase I) is to extend the method to molecular dynamics samples of linear and cyclic peptides with side chains in water. We shall study the cyclic peptide (Ala-Pro-D-Phe)2 in vacuum and in the crystal, decaalanine in water, in both helical and hairpin states and the neuro peptide gonadotropin releasing hormone (GnRH). The long term goal is to further extend the local states method to larger systems such as protein-ligand complexes and to general problems of protein folding. This important toll will be added to the Insight- Discover software package of Biosym Technologies, Inc.

测定多肽和蛋白质的生物活性，以 在很大程度上是由其空间结构决定的。 因此，计算 自由能F很重要，因为最小F是 构象稳定性 然而，通过通常的模拟， F的技术计算是困难的。 “地方政府方法” Meirovitch建议的是一个程序，使人们能够提取F 从计算机模拟样本;它是独立于其他 技术（如热力学积分方法），并具有 本方法具有以下优点：1）适用于任何链条 柔性、稳定状态以及随机卷曲或 这两种极端情况的混合，以及2）它可以用来获得 两个状态之间的Δ F具有很大的结构差异。 的 局域态方法已成功地应用于格点模型 以及十甘氨酸的真实连续模型。 我们的短期 目标（第一阶段）是将该方法扩展到分子动力学样本 线性和环状肽与侧链在水中。 我们将 环肽（Ala-Pro-D-Phe）_2在真空中和在 晶体，十丙氨酸在水中，在螺旋和发夹状态， 神经肽促性腺激素释放激素（GnRH）。 长 长期目标是进一步扩展局部状态方法， 系统，如蛋白质-配体复合物，并涉及 蛋白质折叠 这个重要的收费将被添加到洞察力- 了解Biosym Technologies，Inc.的软件包