The TINKER Modeling Software for Biomolecular Simulation

用于生物分子模拟的 TINKER 建模软件

• 批准号: 6906910
• 负责人: JAY PONDER
• 金额: $ 25.62万
• 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/6906910
• 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.

TINKER 分子建模软件包是一套模块化、可扩展的计算生物学 旨在作为经验势（“力场”）和算法开发的测试平台的程序。 TINKER 以可执行文件和源代码形式免费提供，并在全球学术和工业实验室中得到广泛使用。该软件包的一项重要功能是能够使用许多替代的当代力场参数集进行能量计算。当前的项目打算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。 TINKER 的 Force Field Explorer 图形界面的进一步开发将使 静电效应的可视化，例如极化，以及 TINKER 计算的远程监控。分布式内存并行化、先进的 Ewald 求和方法以及其他代码优化将允许在商品 Beowulf 集群和类似计算机硬件上有效地使用 TINKER。 力场是源自化学物理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”软件可用于各种研究和教育环境。该项目的主要目标是产生一个“下一代”能量模型，该模型将通常为配体结合的热力学和分子内生物聚合物相互作用提供 0.5 kcal/mol 或更好的“化学精度”。特别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改进。这 AMOEBA 可极化原子多极模型可以灵活、准确地描述潜在的永久静电和对分子环境的响应，该模型将扩展到核酸。已记录的源代码和参数的现成可用性将使新的极化势能够合并到其他广泛使用的建模套件中。应用将集中于具有生物学重要性的系统中绝对结合常数的计算、蛋白质环建模、侧链旋转异构体预测和结构精修。含离子系统的结构和能量学也将得到研究，因为人们普遍认为极化在离子通过膜蛋白通道的传输、离子迁移率和 DNA 凹槽中的浓度等问题中发挥着关键作用。