CHARMM-GUI Development for Biomolecular Modeling and Simulation Community

项目摘要/摘要 经过13年的开发和维护，CHARMM-GUIUS(http://www.charmm-gui.org) 已经成为基于Web的复杂生物分子模拟交互构建的重要资源 系统及其输入的准备，具有良好的和可重复的状态模拟协议 使用广泛使用的程序，如CHARMM，NAMD，GROMACS，AMBER， Genesis、Tinker、LAMMPS、Desmond和OpenMM。CHARMM-图形用户界面还显著降低了 学习曲线，防止非专家(例如，实验者)利用建模和模拟进行研究 他们的系统。在此应用程序中，遵循CHARMM-GUI用户的请求和广泛的MD模拟 包开发人员，提出了三个具体目标来扩展CHARMM-图形用户界面的功能以支持 更广泛的建模和仿真社区，具有更多样化的力场选择和高级 技巧。具体地说，AIM1将支持更完整的相加和可极化力场列表，适用于所有- 和联合原子模拟。目标2是开发用于QM和QM/MM计算的QM/MM接口程序。最后， AIM 3将使用基于SILCS的非CHARMM隐式溶剂模型扩展CHARMM-图形用户界面的功能 模拟(通过配基竞争饱和进行位点识别)、配基结合自由能计算、 恒定pH模拟、复制品交换模拟、离子传输模拟、定向/导向模拟、 和路径采样。拟议项目的成功完成预计将提供一个有效的项目- 为生物医学研究界停止在线资源，进行创新和新颖的生物分子建模 以及用于预防和治疗人类疾病的模拟研究。

PROJECT SUMMARY/ABSTRACT Through the development and maintenance over the past 13 years, CHARMM-GUI (http://www.charmm-gui.org) has become an essential web-based resource for the interactive construction of complex biomolecular simulation systems and the preparation of their inputs with well-established and reproducible simulation protocols for state- of-the-art molecular simulations using widely used programs, such as CHARMM, NAMD, GROMACS, AMBER, GENESIS, TINKER, LAMMPS, Desmond, and OpenMM. CHARMM-GUI has also significantly reduced the learning curve that prevents non-experts (e.g., experimentalists) from utilizing modeling and simulation to study their systems. In this application, following requests from CHARMM-GUI users and broad MD simulation package developers, three specific aims are proposed to extend the functionality of CHARMM-GUI to support a broader range of modeling and simulation community with more diverse force field selection and advanced techniques. Specifically, AIM1 is to support a more complete list of additive and polarizable force fields for all- and united-atom simulations. AIM 2 is to develop QM/MM Interfacer for QM and QM/MM calculations. Finally, AIM 3 will extend the functionality of CHARMM-GUI with non-CHARMM implicit solvent models, SILCS-based simulations (Site Identification by Ligand Competitive Saturation), ligand binding free energy calculations, constant pH simulations, replica-exchange simulations, ion transport simulations, targeted/steered simulations, and path sampling. The successful completion of the proposed project is expected to provide an effective one- stop online resource for biomedical research community to carry out innovative and novel biomolecular modeling and simulation research for the prevention and treatment of human disease.