APBS: NANOSCALE BIOMOLECULAR ELECTROSTATICS SOFTWARE

描述(申请人提供)：该项目的目标是通过支持开放源码的自适应泊松-玻尔兹曼解算器和PDB2PQR软件包的维护和继续开发，使在生物医学研究中能够研究大分子的挽救和静电性质。了解静电相互作用对于研究生物分子过程是至关重要的。通过结构基因组学和其他努力，蛋白质和其他生物聚合物的结构正在以越来越快的速度被确定，而这些生物聚合物在细胞途径或超分子组合中的特定联系正在通过遗传和蛋白质组学研究而被发现。为了将这些信息集成到用于药物发现或其他应用的物理模型中，需要能够评估生物聚合物内部和之间的能量相互作用。在分子能量的各种成分中，拯救性质和静电相互作用是特别重要的，因为这些相互作用的范围很长，并且典型的生物聚合物成分具有很大的电荷。APBS是一个独特的软件包，用于求解生物大分子组装的连续介质静电方程。该软件是使用现代设计原则“从头开始”设计的，以确保其与其他计算程序包的接口能力，并随着方法和应用程序的变化而发展。APBS代码附带面向用户和程序员的大量文档，并得到各种用于准备计算和分析结果的实用程序的支持。最后，免费、开源的APBS许可证确保了它对整个生物医学社区的可访问性。使用连续介质拯救方法，如APBS，需要准确和完整的结构数据以及诸如原子电荷和半径等力场参数。不幸的是，连续统静电计算中的限制步骤往往是将蛋白质数据库中缺失的原子坐标添加到分子结构中，并为这些结构分配参数。为了解决这个问题，我们开发了PDB2PQR。该服务器自动执行许多常见的任务，即为连续统拯救计算以及许多其他类型的生物分子结构建模、分析和模拟准备结构。这种自动化允许任何非专家将PDB文件转换为可用于更复杂分析的格式。与APB一样，PDB2PQR也是在开源许可下分发的，以方便世界各地的生物医学研究人员使用它。公共卫生相关性：对静电相互作用的了解对于研究生物分子尺度的过程至关重要，而生物分子尺度的过程对于理解基本的生物过程和进行合理的疾病治疗是基本的。静电学在所有基本的分子尺度现象中扮演着重要的角色，因此对于生物分子结构和相互作用的分析是不可或缺的，包括与健康相关的蛋白质突变的研究和新分子疗法的设计。该项目的目标是通过支持开放源码的自适应泊松-玻尔兹曼解算器和PDB2PQR软件包的维护和继续开发，使生物医学研究中的大分子拯救和静电性质的研究成为可能。

DESCRIPTION (provided by applicant): The goal of this project is to enable the investigation of the salvation and electrostatic properties of macromolecules in biomedical research by supporting the maintenance and continued development of the open-source Adaptive Poisson- Boltzmann Solver and PDB2PQR software packages. An understanding of electrostatic interactions is essential for the study of biomolecular processes. The structures of proteins and other biopolymers are being determined at an increasing rate through structural genomics and other efforts while specific linkages of these biopolymers in cellular pathways or supramolecular assemblages are being detected by genetic and proteomic studies. To integrate this information in physical models for drug discovery or other applications requires the ability to evaluate the energetic interactions within and between biopolymers. Among the various components of molecular energetic, salvation properties and electrostatic interactions are of special importance due to the long range of these interactions and the substantial charges of typical biopolymer components. APBS is a unique software package which solves the equations of continuum electrostatics for large biomolecular assemblages. This software was designed "from the ground up" using modern design principles to ensure its ability to interface with other computational packages and evolve as methods and applications change over time. The APBS code is accompanied by extensive documentation for both users and programmers and is supported by a variety of utilities for preparing calculations and analyzing results. Finally, the free, open-source APBS license ensures its accessibility to the entire biomedical community. The use of continuum salvation methods such as APBS requires accurate and complete structural data as well as force field parameters such as atomic charges and radii. Unfortunately, the limiting step in continuum electrostatics calculations is often the addition of missing atomic coordinates to molecular structures from the Protein Data Bank and the assignment of parameters to these structures. To address this problem, we have developed PDB2PQR. This server automates many of the common tasks of preparing structures for continuum salvation calculations as well as many other types of biomolecular structure modeling, analysis, and simulation. This automation allows any non-expert to convert PDB files into formats that can be used for more complex analyses. Like APBS, PDB2PQR is also distributed under an open source license to facilitate its use by biomedical researchers everywhere. PUBLIC HEALTH RELEVANCE: An understanding of electrostatic interactions is essential for the study of the biomolecular-scale processes that are fundamental to understanding basic biological processes and undertaking the rational treatment of disease. Electrostatics plays an important role in all basic molecular-scale phenomena and therefore is integral to the analysis of biomolecular structure and interactions, including the study of health-related protein mutations and design of new molecular therapies. The goal of this project is to enable the investigation of the salvation and electrostatic properties of macromolecules in biomedical re- search by supporting the maintenance and continued development of the open-source Adaptive Poisson-Boltzmann Solver and PDB2PQR software packages.