Modeling Aqueous Solvation in Biology

生物学中的水溶剂化建模

• 批准号: 7282433
• 负责人: Ken A Dill
• 金额: $ 25.77万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-09-01 至 2009-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7282433
• 关键词: Area; Biological; Biology; Cells; Charge; Complex; Computational Biology; Computer Simulation; Crowding; Development; Dill; Electrostatics; Environment; Equation; Free Energy; Goals; Hydrogen Bonding; Hydrophobicity; Lead; Learning; Ligands; Methods; Modeling; Nature; Particulate; Physics; Pyrococcus kodakaraensis TIP protein; Slovenia; Solvents; Surface; Thermodynamics; Water; Work; analytical method; aqueous; base; carbene; density; macromolecule; molecular dynamics; repaired; theories

DESCRIPTION (provided by applicant): Ken Dill (UCSF) and Vojko Vlachy (Slovenia) are collaborating to develop physics-based models of water and aqueous solvation. Currently, there are two choices for computational modeling of solvent: (1) Explicit solvent models - TIP, SPC, etc., which are computationally too expensive for many applications. (2) Implicit solvent models - Poisson-Boltzmann (PB) or Generalized Born (GB), which replace water molecules with a continuum. PB or GB models often give incorrect free energies because they miss the hydrogen bonding, the particulate nature of water, and effects of surface geometry. Here, we propose a third approach: we are treating water molecules and hydrogen bonding explicitly, but with analytical methods - integral equations, thermodynamic perturbation theory, density functional theory, and mean-field models - that are computationally efficient. In preliminary work, these methods are already 3 orders of magnitude faster to compute, and they correct several of the flaws of simpler models. If successful, the developments here would lead to better ways to handle solvation in computational biology.

描述（由申请人提供）：Ken Dill（UCSF）和Vojko Vlachy（斯洛文尼亚）正在合作开发基于物理的水和水溶剂化模型。目前，溶剂的计算模型有两种选择：（1）显式溶剂模型- TIP，SPC等，这对于许多应用来说在计算上太昂贵。(2)隐式溶剂模型-泊松-玻尔兹曼（PB）或广义玻恩（GB），用连续介质代替水分子。PB或GB模型经常给出不正确的自由能，因为它们错过了氢键，水的颗粒性质和表面几何形状的影响。 在这里，我们提出了第三种方法：我们明确地处理水分子和氢键，但使用计算效率高的分析方法--积分方程、热力学微扰理论、密度泛函理论和平均场模型。在初步工作中，这些方法的计算速度已经快了3个数量级，并且它们纠正了简单模型的一些缺陷。如果成功，这里的发展将导致更好的方法来处理计算生物学中的溶剂化。