DelPhi: Software for Electrostatic Modeling of Biomolecules and Objects

DelPhi：生物分子和物体静电建模软件

• 批准号: 8520333
• 负责人: Emil Georgiev Alexov
• 金额: $ 38.99万
• 依托单位: CLEMSON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-08-10 至 2015-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8520333
• 关键词: Algorithms; Amino Acids; Binding; Biological; Biological Models; Biological Process; Charge; Code; Communities; Computer Systems; Computer software; DNA; Dependence; Development; Dimensions; Drug Receptors; Educational workshop; Electrostatics; Ensure; Equation; Free Energy; Funding; Goals; Health; High Performance Computing; Human; Ionic Strengths; Ions; Maintenance; Manuals; Maps; Marketing; Membrane; Metals; Modeling; Nanotechnology; Nature; Operating System; Output; Phase; Probability; Process; Programming Languages; Proteins; RNA; Research; Research Personnel; Resolution; Role; Shapes; Sodium Chloride; Solutions; Source Code; Space Models; Specialist; Specificity; Speed; Structure; Surface; System; Testing; Water; Work; computing resources; drug discovery; indexing; macromolecule; nanodevice; nanosystems; public health relevance; three dimensional structure; tool; user-friendly; web page; wiki

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.

描述（由申请人提供）：本项目的目标是维护和进一步开发现有软件德尔菲（http：//wiki.c2b2.columbia.edu/honiglab_public/index.php/Software：DelPhi）。德尔菲提供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。静电的作用有两个方面：提供长程相互作用，使生物分子转向其预结合方向，并通过强短程直接相互作用促进特异性。此外，许多生物学上重要的效应，如pH和盐依赖性效应，主要是静电性质。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发生在纳米系统和纳米器件中的许多其他现象至关重要。 我们建议维护和进一步开发德尔菲，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到不同的空间区域，建模几何对象和电荷分布，处理系统含有混合盐溶液，我们计划开发新的选项，作为建模隐式/显式膜，预测显式离子结合和新的几何对象。与此同时，我们将使代码和相应的算法现代化，并促进与用户的互动。 公共卫生相关性：静电对于几乎所有生物大分子的功能、稳定性和相互作用（包括受体-药物识别）是必不可少的。静电的中心作用是由于大多数生物大分子是高度带电的，因为它们含有许多带电的氨基酸，这些氨基酸反过来对各种生物分子的结构，功能和相互作用至关重要。许多重要的生物效应，如pH值和盐依赖性效应，主要是静电性质。因此，静电势和相应能量的准确建模对于成功的药物发现和优化至关重要。