Through the development and maintenance over the past 13 years, CHARMM-GUI (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.
(RELEVANCE) The proposed research will help expert and non-expert researchers from a broader range of modeling and simulation community to build complex biomolecular systems of their interests and prepare the input files for any general and advanced modeling and simulation through the large and unique scope of CHARMM-GUI functionality. Therefore, they can carry out innovative and novel biomedical modeling and simulation research, which will enrich our understanding of pathological mechanisms underlying major human diseases, and thus eventually facilitate the development of effective therapeutic agents to treat human disease.
