The TINKER Modeling Software for Biomolecular Simulation

TINKER分子建模软件包是一个模块化的，可扩展的计算生物学 这些程序旨在作为经验势（“力场”）和算法开发的测试平台。TINKER以可执行代码和源代码的形式免费提供，并在全球的学术和工业实验室中广泛使用。该软件包的一个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。目前的项目打算将这种比较能力扩展到生物分子模拟的新兴极化能量模型。力场探测器图形界面的进一步开发将使TINKER 静电效应的可视化，如极化，以及TINKER计算的远程监控。分布式内存并行化，先进的埃瓦尔德求和方法和其他代码优化将允许在商品Beowulf集群和类似的计算机硬件上有效地使用TINKER。 力场是从化学物理学的经典原理衍生出的大量原子级生物分子建模技术的基石。因此，“分子力学”软件在各种研究和教育环境中使用。这个项目的主要目标是产生一个“下一代”的能量模型，将定期提供“化学精度”为0.5千卡/摩尔或更好的配体结合的热力学和分子内生物聚合物相互作用。基于结构的药物设计和高分辨率同源建模，特别是，将受益于由此产生的准确性的提高。的 AMOEBA极化原子多极模型，它提供了一个灵活和准确的描述潜在的永久静电和分子环境的响应，将扩展到核酸。文档化的源代码和参数的现成可用性将使新的极化潜力纳入其他广泛使用的建模套件。应用程序将集中在生物学重要性，蛋白质环建模，侧链旋转异构体预测和结构优化系统的绝对结合常数的计算。含离子系统的结构和能量学也将被研究，因为极化被广泛认为在诸如通过膜蛋白通道的离子运输、离子迁移率和DNA凹槽中的浓度等问题中起关键作用。

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.