The TINKER Modeling Software for Biomoledular Simulation

用于生物分子模拟的 TINKER 建模软件

• 批准号: 7036574
• 负责人: JAY PONDER
• 金额: $ 26.15万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-04-01 至 2009-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7036574
• 关键词: bioengineering /biomedical engineering; biophysics; chemical models; computational biology; computer program /software; computer system design /evaluation; electric field; intermolecular interaction; mathematics; molecular dynamics; protein structure; thermodynamics; tissue engineering

The TINKER Molecular Modeling package is a modular, extensible set of computational biology programs intended to serve as a test-bed for empirical potentials ("force fields") and algorithm development. TINKER is freely available in both executable and source code form, and has seen extensive use in both academic and industrial labs worldwide. An important capability of the package is its ability to perform energy calculations with a number of alternative present-generation force field parameter sets. The current project intends to extend this comparative capability to emerging polarizable energy models for biomolecular simulation. Further development of the Force Field Explorer graphical interface to TINKER will enable visualization of electrostatic effects, such as polarization, and remote monitoring of TINKER calculations. Distributed memory parallelization, advanced Ewald summation methods, and other code optimizations will allow efficient use of TINKER on commodity Beowulf clusters and similar computer hardware. Force fields are the cornerstone of a vast array of atomic-level biomolecular modeling techniques derived from classical principles of chemical physics. As such, "molecular mechanics" software sees use in a variety of research and educational settings. A primary goal of this project is to produce a "next-generation" energy model that will routinely provide "chemical accuracy" of 0.5 kcal/mol or better for the thermodynamics of ligand binding and for intramolecular biopolymer interactions. Structure-based drug design and highresolution homology modeling, in particular, will benefit from the resulting accuracy improvements. The AMOEBA polarizable atomic multipole model, which provides a flexible and accurate description of the underlying permanent electrostatics and response to the molecular environment, will be extended to nucleic acids. The ready availability of documented source code and parameters will enable the incorporation of the new polarizable potential into other widely-used modeling suites. Applications will focus on calculation of absolute binding constants in systems of biological importance, protein loop modeling, side chain rotamer prediction and structure refinement. The structure and energetics of ion-containing systems will also be investigated, since polarization is widely considered to play a key role in problems such as ion transport through membrane protein channels, ion mobility and concentration in DNA grooves.

修补匠分子建模包是一组模块化的计算生物学集 旨在作为经验潜力（“力场”）和算法开发的测试床的计划。 Tinker以可执行文件和源代码表可以自由使用，并且在全球的学术和工业实验室中都广泛使用。包装的一个重要能力是它具有许多替代造成生成力场参数集的能量计算的能力。当前的项目旨在将这种比较能力扩展到用于生物分子模拟的新兴极化能量模型。进一步开发到林格的力场探索器图形接口将启用 静电效应的可视化，例如极化和修补程序计算的远程监测。分布式内存并行化，高级ewald求和方法和其他代码优化将使在商品beowulf群集和类似的计算机硬件上有效使用修补匠。 力场是源自化学物理学经典原理的大量原子级生物分子建模技术的基石。因此，“分子力学”软件可在各种研究和教育环境中使用。该项目的主要目标是产生“下一代”能量模型，该模型通常提供0.5 kcal/mol的“化学精度”，或者用于配体结合的热力学和分子内生物聚合物相互作用。尤其是基于结构的药物设计和高分辨率同源建模将受益于由此产生的准确性提高。这 Amoeba极化原子多极模型将扩展到核酸，从而对潜在的永久性静电和对分子环境的响应进行柔性且准确的描述。现成的源代码和参数的现成可用性将使新的两极分化潜力纳入其他广泛使用的建模套件中。应用将集中于在生物学重要性，蛋白质环建模，侧链旋转旋转器预测和结构改进系统中的绝对结合常数计算。还将研究含离子系统的结构和能量学，因为极化被认为在通过膜蛋白通道，离子迁移率和DNA凹槽中的离子迁移率和浓度等问题中起着关键作用。