CHARMM-GUI Development for Biomolecular Modeling and Simulation Community

项目总结/摘要 经过13年的开发和维护，CHARMM-GUI（http：www.charmm-gui.org） 已经成为复杂生物分子模拟交互式构建的重要网络资源 系统及其输入的准备与完善的和可重复的模拟协议的状态， 使用广泛使用的程序，如CHARMM，NAMD，GROMACS，AMBER， GENESIS、TINKER、LAMMPS、Desmond和OpenMM。CHARMM-GUI还大大减少了 防止非专家（例如，实验者）从利用建模和仿真来研究 他们的系统。在此应用中，根据CHARMM-GUI用户和广泛MD模拟的要求， 包开发人员提出了三个具体目标来扩展CHARMM-GUI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先进的 技术.具体来说，AIM 1是支持所有加性和可极化力场的更完整列表- 和联合原子模拟。目标2是开发QM/MM接口，用于QM和QM/MM计算。最后， AIM 3将扩展CHARMM-GUI的功能，使用非CHARMM隐式溶剂模型、基于SILCS的 模拟（通过配体竞争饱和度的位点鉴定），配体结合自由能计算， 恒定pH模拟，复制交换模拟，离子传输模拟，靶向/转向模拟， 和路径采样。拟议项目的顺利完成预计将提供一个有效的- 停止生物医学研究社区在线资源，以进行创新和新颖的生物分子建模 以及人类疾病防治的模拟研究。

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.