Modeling Aqueous Solvation in 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液模型。目前，溶剂的计算建模有两种选择：(1)显式溶剂模型- TIP， SPC等，对于许多应用来说，这些模型在计算上过于昂贵。(2)隐式溶剂模型——泊松-玻尔兹曼模型（PB）或广义玻恩模型（GB），用连续体代替水分子。PB或GB模型通常给出不正确的自由能，因为它们忽略了氢键、水的颗粒性质和表面几何形状的影响。

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.