GCMC_PME

The oscillating chemical potential GCMC method was extended to include treatment of long-range electrostatic interactions improving the treatment of ions using the GCMC approach. Included are executables as well as the original code. To date, in the MacKerell lab the method has been applied primarily to RNA, though the approach is applicable to performing GCMC solute sampling in a range of systems including proteins and bilayers.

Source code available in directory: gcmc_pme_source_code

Publications related to source code:

• Lakkaraju, S.K., Raman, E.P., Yu, W., and MacKerell, A.D., Jr., “Sampling of Organic Solutes in Aqueous and Heterogeneous Environments using Oscillating μex Grand Canonical-like Monte Carlo-Molecular Dynamics Simulations,” Journal of Chemical Theory and Computing, 10: 2281–2290, 2014, 10.1021/ct500201y, PMC4053307

• Sun, D., Lakkaraju, K., Jo, S., and MacKerell, A.D., Jr., “Determination of Ionic Hydration Free Energies with Grand Canonical Monte Carlo/Molecular Dynamics Simulations in Explicit Water,” Journal of Chemical Theory and Computation, 14: 5290-5302, 2018, 10.1021/acs.jctc.8b00604, PMC6195813

RNA-Mg-Predictor : Application of GCMC_PME code

The scripts in this directory can be used to setup a GCMC-MD simulation to identify the Mg2+ and K+ binding sites in RNA molecules. It has been provided in the form to be applied to native states of RNA, however it has also been applied to study ion-atomsphere during the folding of RNA in the following articles.

The two modifications to gcmc_pme code used in this application are:

• rna-mg-predictor/bin/mod_swap_gcmc (Source: gcmc_pme_source_code/gcmc_pme_with_hard_limit_option_only_ins-del)

• rna-mg-predictor/bin/mod_equi_gcmc (Source: gcmc_pme_source_code/gcmc_pme_with_hard_limit_option_only_rot-tra)

Publications related to rna-mg-predictor scripts:

• Kognole, A.A. and MacKerell, A.D., Jr., “Mg2+ Impacts the Twister Ribozyme through Push-Pull Stabilization of Non-Sequential Phosphate Pairs,” Biophysical Journal, 6: 1424-1437, 2020, 10.1016/j.bpj.2020.01.021, PMC7091459

• Kognole, A.A. and MacKerell, A.D., Jr., “Contributions and competition of Mg2+ and K+ in folding and stabilization of the Twister Ribozyme,” RNA, 26:1704-1715, 2020, 10.1261/rna.076851.120, PMC7566569

Additional packages that are required for the RNA example.

• GROMACS (https://github.com/gromacs/gromacs)
• OpenMM with CUDA (conda install -c conda-forge openmm)
• Plumed plugin for OpenMM (conda install -c conda-forge openmm-plumed)
• ParmEd to utilize the GROMACS formats in OpenMM (conda install -c omnia parmed)
• MMTSB Toolset to manupulate the PDB files (installed on-the-fly from github)
• MDAnalysis to run clustering analysis (conda install -c conda-forge mdanalysis)

To run simply run the bash scripts in the order:

1. 01_setup.sh
2. 02_run.sh
3. 03_analyze.sh
4. 04_compress.sh