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开发现有的软件德尔福(http://wiki.c2b2.columbia.edu/honiglab_public/index.php/Software:DelPhi).Delphi提供Poisson-Boltzmann方程(PBE)(线性和非线性形式)的数值解，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。静电学的作用有两个方面：提供长程相互作用，引导生物分子走向它们的结合前取向，以及通过强烈的短程直接相互作用来促进特异性。此外，许多重要的生物学效应，如pH和盐依赖效应，本质上主要是静电。此外，纳米技术的不断进步要求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，准确计算静电场和能量对于成功模拟纳米系统和纳米设备中发生的几乎所有生物过程和许多其他现象至关重要。我们建议保留和进一步开发Delphi，这是许多研究人员使用的第一个PB求解器，如提案的主体所示。除了现有的功能，如分配不同的介电常数给不同的空间区域，模拟几何对象和电荷分布，处理含有混合盐溶液的体系，我们计划开发新的选择，如模拟隐式/显式膜，预测显式离子结合和新的几何对象。同时，我们将使代码和相应的算法现代化，并将促进与我们的用户的互动。 公共卫生相关性：静电学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，包括受体-药物识别。静电学的核心作用是由于大多数生物大分子都是高度带电的，因为它们含有许多带电氨基酸，这些氨基酸反过来对各种生物分子的结构、功能和相互作用是必不可少的。许多重要的生物学效应，如pH和盐依赖效应，本质上主要是静电。因此，对静电势和相应的能量进行准确的建模对于成功的药物发现和优化至关重要。

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.