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

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TitleCHARMM additive and polarizable force fields for biophysics and computer-aided drug design.
Publication TypeJournal Article
Year of Publication2015
AuthorsVanommeslaeghe, K, Mackerell, AD
JournalBiochim Biophys Acta
Volume1850
Issue5
Pagination861-71
Date Published2015 May
ISSN0006-3002
KeywordsAnisotropy, Carbohydrate Conformation, Carbohydrates, Computer-Aided Design, Drug Design, Ligands, Lipids, Molecular Docking Simulation, Molecular Dynamics Simulation, Molecular Structure, Nucleic Acid Conformation, Nucleic Acids, Pharmaceutical Preparations, Protein Conformation, Proteins, Static Electricity, Structure-Activity Relationship, Surface Properties
Abstract

BACKGROUND: 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.

SCOPE OF REVIEW: 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.

MAJOR CONCLUSIONS: 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.

GENERAL SIGNIFICANCE: 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".

DOI10.1016/j.bbagen.2014.08.004
Alternate JournalBiochim. Biophys. Acta
PubMed ID25149274
PubMed Central IDPMC4334745
Grant ListR01 GM072558 / GM / NIGMS NIH HHS / United States
R01 GM070855 / GM / NIGMS NIH HHS / United States
GM051501 / GM / NIGMS NIH HHS / United States
GM070855 / GM / NIGMS NIH HHS / United States
R01 GM051501 / GM / NIGMS NIH HHS / United States
R29 GM051501 / GM / NIGMS NIH HHS / United States
GM072558 / GM / NIGMS NIH HHS / United States