DelPhi: Software for Electrostatic Modeling of Biomolecules and Objects

描述（由申请人提供）：该项目的目标是维护和进一步发展现有的软件DelPhi （http://wiki.c2b2.columbia.edu/honiglab_public/index.php/Software:DelPhi）。DelPhi提供泊松-玻尔兹曼方程（PBE）的数值解（线性和非线性形式），并计算浸入水和盐相或其他连续介质中的分子和几何物体的相应能量。静电力对于几乎所有生物大分子的功能、稳定性和相互作用都是必不可少的，因为大多数生物大分子，特别是DNA和RNA，都是高度带电的。静电的作用是双重的：提供远程相互作用，引导生物分子向其结合前的方向，并通过强的短程直接相互作用促进特异性。此外，许多重要的生物学效应，如pH和盐依赖效应，在自然界中主要是静电作用。此外，纳米技术的不断进步需要对由生物分子和带电金属/电介质表面和物体组成的系统进行建模。因此，静电场和能量的精确计算对于成功模拟几乎所有的生物过程和纳米系统和纳米器件中发生的许多其他现象至关重要。我们建议保留并进一步发展DelPhi，这是许多研究人员使用的第一个PB求解器，如提案主体所示。除了现有的功能，如为空间的不同区域分配不同的介电常数，建模几何物体和电荷分布，处理含有混合盐溶液的系统，我们计划开发新的选项，如建模隐式/显式膜，预测显式离子结合和新的几何物体。同时，我们将使代码和相应的算法现代化，并将促进与用户的交互。

DESCRIPTION (provided by applicant): The goal of this project is to maintain and further develop the existing software DelPhi (http://wiki.c2b2.columbia.edu/honiglab_public/index.php/Software:DelPhi). DelPhi provides numerical solutions to the Poisson-Boltzmann Equation (PBE) (both linear and non-linear forms) and calculates the corresponding energies for molecules and geometric objects immersed in water and salt phase or another continuum medium. Electrostatic forces are essential for the function, stability and interactions of virtually all biological macromolecules because most biological macromolecules, especially DNA and RNA, are highly charged. The role of electrostatics is two fold: providing long-range interactions steering biological molecules toward their pre-binding orientations and contributing to the specificity by strong short-range direct interactions. In addition, many biologically important effects such as pH and salt dependence effects are primarily electrostatic in nature. Moreover, the constant progress of nanotechnology requires modeling of systems made of biological molecules and charged metal/dielectric surfaces and objects. Thus, accurate calculations of electrostatic fields and energies are crucial for successful modeling of virtually all biological processes and many other phenomena occurring in nanosystems and nanodevices. We propose to maintain and further develop the DelPhi, the first PB solver used by many researchers as is shown in the main body of the proposal. In addition to the existing features such as assigning different dielectric constants to different regions of space, modeling geometrical objects and charge distributions, treating systems containing mixed salt solutions, we plan to develop new options as modeling implicit/explicit membrane, predicting explicit ion binding and new geometrical objects. In parallel we will modernize the code and the corresponding algorithms and will facilitate interactions with our users. PUBLIC HEALTH RELEVANCE: Electrostatics is essential for function, stability and interactions of virtually all biological macromolecules, including receptor-drug recognition. The central role of electrostatics is due to the fact that most biological macromolecules are highly charged, because they contain many charged amino acids which in turn are essential for structure, function and interactions of variety of biomolecules. Many biologically important effects such as pH and salt dependence effects are primarily electrostatic in nature. Therefore an accurate modeling of electrostatic potential and the corresponding energies is critical for successful drug discovery and optimization.