CHARMM: The biomolecular simulation program

Abstract

CHARMM (Chemistry at HARvard Molecular Mechanics) is a highly versatile and widely used molecular simulation program. It has been developed over the last three decades with a primary focus on molecules of biological interest, including proteins, peptides, lipids, nucleic acids, carbohydrates and small molecule ligands, as they occur in solution, crystals, and membrane environments. For the study of such systems, the program provides a large suite of computational tools that include numerous conformational and path sampling methods, free energy estimators, molecular minimization, dynamics, and analysis techniques, and model-building capabilities. In addition, the CHARMM program is applicable to problems involving a much broader class of many-particle systems. Calculations with CHARMM can be performed using a number of different energy functions and models, from mixed quantum mechanical-molecular mechanical force fields, to all-atom classical potential energy functions with explicit solvent and various boundary conditions, to implicit solvent and membrane models. The program has been ported to numerous platforms in both serial and parallel architectures. This paper provides an overview of the program as it exists today with an emphasis on developments since the publication of the original CHARMM paper in 1983.

Comment on “On using a too large integration time step in molecular dynamics simulations of coarse-grained molecular models” by M. Winger, D. Trzesniak, R. Baron and W. F. van Gunsteren, Phys. Chem. Chem. Phys., 2009, 11, 1934

“…The issue of the calculation of velocity-dependent properties in the Leap-frog scheme is also discussed by Cuendet and van Gunsteren, 9 with the suggestion to use the average kinetic energy (as implemented in GROMACS) rather than the average of the velocities (GROMOS) in MD simulation. A similar problem is noted with CHARMM, 10 reporting a temperature that does not reflect the actual temperature in simulations when using large time-steps (see ESI for details). Based on the two arguments discussed above, we conclude that time steps exceeding 10 fs can be used in the MARTINI force field, and possibly also in combination with other CG force fields that use a similar degree of coarse-graining.…”

Identification and characterization of novel mutations implicated in congenital fibrinogen disorders

“…Structures of the γ and Bβ chain mutants were constructed by altering the relevant wild‐type residues to the mutant form within Discovery Studio. Predicted mutation‐induced changes in energy and/or protein conformation of the fibrinogen complex and the fragment D dimer were determined by subjecting the wild‐type and mutant structures to solvent‐based energy minimization using the smart minimization protocol with a CHARMM forcefield21 and the Generalized Born with Simple Switching (GBSW) implicit solvent model 22. Predicted protein–protein interactions between the minimized wild‐type and/or mutant fibrinogen fragment D structures were calculated using the ZDock algorithm 23.…”

Discovery of Plasmepsin Inhibitors by Fragment‐Based Docking and Consensus Scoring

“…Hydrogen positions were optimized by energy minimization with the computer program CHARMM [30,31], using 100 steps of steepest descent and 10000 steps of conjugate gradient minimization.…”