Collaborative Research: Development and Application of the AMOEBA Polarizable Force Field

华盛顿大学圣刘易斯分校的杰伊·庞德和圣刘易斯大学的大卫·戈哈拉得到了化学系化学理论、模型和计算方法项目的支持，和网络基础设施办公室，以提高AMOEBA的准确性生物分子应用的原子多极优化能量学力场模型的分子模拟，并通过并行化的基础TINKER分子模拟软件，增加模型的适用范围。 在这个项目中，研究人员为AMOEBA-2模型开发了新的术语，包括原始AMOEBA力场中缺失的物理效应。特别是，电荷转移，穿透效应和阻尼短程色散项正在参数化，以消除最大的剩余系统的不准确性。将由此产生的短程能量模型与量子力学计算进行比较，可以将内部能量正确地划分为各个项，并为改进AMOEBA-2提供一致的基础。现有的TINKER代码以及新的能源条款正在使用混合的OpenMP和MPI范式并行化。由此产生的新的潜力和软件将被应用到目前的两个问题，需要广泛的模拟和高水平的准确性：预测有机晶体结构，并计算在主-客体复合物中的配体结合。这两个问题长期以来都是计算化学领域的“圣杯”应用。分子力场计算是计算生物物理、生物大分子结构确定、分子设计以及分子和材料性质建模的重要工具。通过定期发布TINKER分子建模包的新版本，在该项目下开发的方法，算法和软件可供更广泛的社区使用。该软件包广泛应用于世界各地的学术研究实验室以及化学和制药行业。该小组还通过大学课程参与教育活动，并为希望在自己的教学中使用TINKER软件的教师提供辅导材料和实验练习。

Jay Ponder of Washington University in Saint Louis and David Gohara of Saint Louis University are supported by an award from the Chemical Theory, Models and Computational Methods program in the Division of Chemistry, and the Office of Cyberinfrastructure to improve the accuracy of the AMOEBA (Atomic Multipole Optimized Energetics for Biomolecular Applications) force field model for molecular simulation and to increase the range of applicability of the model via parallelization of the underlying TINKER molecular modeling software. In this project, the researchers develop new terms for an AMOEBA-2 model that encompass physical effects missing from the original AMOEBA force field. In particular, charge transfer, penetration effects and damped short-range dispersion terms are being parameterized to remove the largest remaining systematic inaccuracies. Comparison of the resulting short-range energetic model against quantum mechanical calculations allow correct partitioning of internal energy into the various terms, and provide a consistent basis for improving AMOEBA-2. The existing TINKER code as well as the new energy terms are being parallelized using a hybrid OpenMP and MPI paradigm. The resulting new potential and software will be applied to two current problems that require both extensive simulation and a high level of accuracy: prediction of organic crystal structures, and computation of ligand binding in host-guest complexes. Both of these problem areas have long represented "holy grail" applications for the field of computational chemistry.Molecular force field calculations are important tools in computational biophysics, structure determination of bio-macromolecules, molecular design, and modeling of the properties of molecules and materials. Methods, algorithms and software developed under this project are being made available to the broader community via periodic release of new versions of the TINKER molecular modeling package. This package is widely used in academic research labs and in the chemical and pharmaceutical industries worldwide. The team is also involved in educational activities through University courses, as well as the provision of tutorial materials and laboratory exercises for instructors wishing to use the TINKER software in their own teaching.