A generic implementation of replica exchange with solute tempering (REST2) algorithm in NAMD for complex biophysical simulations

Abstract Replica Exchange with Solute Tempering (REST2) is a powerful sampling enhancement algorithm of molecular dynamics (MD) in that it needs significantly smaller number of replicas but achieves higher sampling efficiency relative to standard temperature exchange algorithm. In this paper, we extend the applicability of REST2 for quantitative biophysical simulations through a robust and generic implementation in greatly scalable MD software NAMD. The rescaling procedure of force field parameters controlling REST2 “hot region” is implemented into NAMD at the source code level. A user can conveniently select hot region through VMD and write the selection information into a PDB file. The rescaling keyword/parameter is written in NAMD Tcl script interface that enables an on-the-fly simulation parameter change. Our implementation of REST2 is within communication-enabled Tcl script built on top of Charm++, thus communication overhead of an exchange attempt is vanishingly small. Such a generic implementation facilitates seamless cooperation between REST2 and other modules of NAMD to provide enhanced sampling for complex biomolecular simulations. Three challenging applications including native REST2 simulation for peptide folding–unfolding transition, free energy perturbation/REST2 for absolute binding affinity of protein–ligand complex and umbrella sampling/REST2 Hamiltonian exchange for free energy landscape calculation were carried out on IBM Blue Gene/Q supercomputer to demonstrate efficacy of REST2 based on the present implementation. Program summary Program title: REST2-NAMD Catalogue identifier: AEXX_v1_0 Program summary URL: http://cpc.cs.qub.ac.uk/summaries/AEXX_v1_0.html Program obtainable from: CPC Program Library, Queen’s University, Belfast, N. Ireland Licensing provisions: Standard CPC licence, http://cpc.cs.qub.ac.uk/licence/licence.html No. of lines in distributed program, including test data, etc.: 240886 No. of bytes in distributed program, including test data, etc.: 8474342 Distribution format: tar.gz Programming language: C/C++, Tcl8.5. Computer: Not computer specific. Operating system: Any. Has the code been vectorized or parallelized?: Yes, MPI and/or PAMI parallelized depending on machine system software; ≥ 8192 cores used on IBM Blue Gene/Q Classification: 3. External routines: NAMD 2.10 ( http://www.ks.uiuc.edu/Research/namd/ ) Nature of problem: A generic implementation providing user-friendly API including input file preparation and performing replica exchange, and high frequency exchange attempt frequency with minimal communication overhead. Solution method: The rescaling procedure of force field parameters controlling REST2 is implemented into NAMD at the source code level. A user can conveniently select hot region through VMD and write the selection information into a PDB file. The rescaling keyword/parameter is written in NAMD Tcl script interface that enables an on-the-fly simulation parameter change. The implementation of REST2 is within communication-enabled Tcl script built on top of Charm++, thus communication overhead of an exchange attempt is vanishingly small. Running time: 30 min–60 min