Generalized scalable multiple copy algorithms for molecular dynamics simulations in NAMD

Abstract

Computational methodologies that couple the dynamical evolution of a set of replicated copies of a system of interest offer powerful and flexible approaches to characterize complex molecular processes. Such multiple copy algorithms (MCAs) can be used to enhance sampling, compute reversible work and free energies, as well as refine transition pathways. Widely used examples of MCAs include temperature and Hamiltonian-tempering replica-exchange molecular dynamics (T-REMD and H-REMD), alchemical free energy perturbation with lambda replica-exchange (FEP/λ-REMD), umbrella sampling with Hamiltonian replica exchange (US/H-REMD), and string method with swarms-of-trajectories conformational transition pathways. Here, we report a robust and general implementation of MCAs for molecular dynamics (MD) simulations in the highly scalable program NAMD built upon the parallel programming system Charm++. Multiple concurrent NAMD instances are launched with internal partitions of Charm++ and located continuously within a single communication world. Messages between NAMD instances are passed by low-level point-to-point communication functions, which are accessible through NAMD’s Tcl scripting interface. The communication-enabled Tcl scripting provides a sustainable application interface for end users to realize generalized MCAs without modifying the source code. Illustrative applications of MCAs with fine-grained inter-copy communication structure, including global lambda exchange in FEP/λ-REMD, window swapping US/H-REMD in multidimensional order parameter space, and string method with swarms-of-trajectories were carried out on IBM Blue Gene/Q to demonstrate the versatility and massive scalability of the present implementation.

Optimized Lennard-Jones Parameters for Druglike Small Molecules

“…38-39 A replica-exchange method 45, 47 was used to enhance the sampling to achieve better convergence. The implementation of the alchemical FEP/REMD 45 into NAMD 48 was utilized for these calculations. The compounds were solvated in a cubic water box of TIP3P water molecules 49 with an edge of 20 Å.…”

Enhanced sampling techniques in molecular dynamics simulations of biological systems

“…Allowing the exchange of the thermodynamic coupling parameter λ also improved the search for alternative conformations of modeled biomolecules [36]. The exchanges along the thermodynamic coupling λ were shown to help distribute the side chain rotamers of a protein in different states [37]. A combination of a dual free energy perturbation (FEP) and λ-REMD was also proposed to be useful for calculation of the absolute binding free energy of p-xylene to a mutant of lysozyme [38].…”

Mapping to Irregular Torus Topologies and Other Techniques for Petascale Biomolecular Simulation

“…They provide a powerful method to characterize complex molecular processes by providing for enhanced sampling, computation of free energies, and refinement of transition pathways. Recently, a robust and generalized implementation of MCAs has been added to NAMD based on the partition framework in Charm++ [18]. …”

“…The Tcl based API serves as a powerful tool because it enables generalized MCAs without any modification to the NAMD source code. NAMD’s MCA implementation has been demonstrated to be massively scalable, in part due to the scalable partition framework of Charm++ [18]. …”