CHARMM additive and polarizable force fields for biophysics and computer-aided drug design

• Published in: Biochimica et biophysica acta Vol. 1850; no. 5; pp. 861 - 871
• Main Authors: Vanommeslaeghe, K., MacKerell, A.D.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.05.2015
• Subjects: Anisotropy; Biophysics; Carbohydrate Conformation; Carbohydrates - chemistry; Computer-Aided Design; Computer-aided drug design; DNA; Drug Design; drugs; Empirical force field; Ligands; lipids; Lipids - chemistry; mechanics; Molecular Docking Simulation; Molecular dynamics; Molecular Dynamics Simulation; Molecular Mechanics; Molecular Structure; Nucleic Acid Conformation; Nucleic Acids - chemistry; Nucleic Acids - metabolism; Pharmaceutical Preparations - chemistry; philosophy; Potential energy function; Protein Conformation; proteins; Proteins - chemistry; Proteins - metabolism; Static Electricity; Structure-Activity Relationship; Surface Properties; Molecular dynamics; Computer-aided drug design; Biophysics; Empirical force field; Potential energy function; Molecular Mechanics
• ISSN: 0304-4165; 0006-3002; 1872-8006
• DOI: 10.1016/j.bbagen.2014.08.004

Molecular Mechanics (MM) is the method of choice for computational studies of biomolecular systems owing to its modest computational cost, which makes it possible to routinely perform molecular dynamics (MD) simulations on chemical systems of biophysical and biomedical relevance. As one of the main factors limiting the accuracy of MD results is the empirical force field used, the present paper offers a review of recent developments in the CHARMM additive force field, one of the most popular biomolecular force fields. Additionally, we present a detailed discussion of the CHARMM Drude polarizable force field, anticipating a growth in the importance and utilization of polarizable force fields in the near future. Throughout the discussion emphasis is placed on the force fields' parametrization philosophy and methodology. Recent improvements in the CHARMM additive force field are mostly related to newly found weaknesses in the previous generation of additive force fields. Beyond the additive approximation is the newly available CHARMM Drude polarizable force field, which allows for MD simulations of up to 1μs on proteins, DNA, lipids and carbohydrates. Addressing the limitations ensures the reliability of the new CHARMM36 additive force field for the types of calculations that are presently coming into routine computational reach while the availability of the Drude polarizable force fields offers an inherently more accurate model of the underlying physical forces driving macromolecular structures and dynamics. This article is part of a Special Issue entitled “Recent developments of molecular dynamics”. •CHARMM36 is a comprehensive force field for simulations of bio- and organic molecules.•Electronic polarizability may be treated using the classical Drude oscillator.•Inclusion of polarizability yields a more accurate description of the physical forces dictating structure and dynamics.