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 bimolecular 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.

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 a model that is an inherently more accurate model of the underlying physical forces driving macromolecular structures and dynamics.

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 CHARMM additive polarizable force fields for biophysics computer-aided drug design algorithms for high-resolution refinement and binding affinity estimation of inhibitors of CGQMCTVWCSSGC targeted conserved peptide substitution mimetic pharmacostructures antagonizing VEGFR-3-mediated oncogenic effects.

Keywords

molecular dynamics, empirical force field, potential energy function, molecular mechanics, computer-aided drug design, biophysics; CHARMM additive; polarizable force fields; biophysics; computer-aided drug design; algorithms; high-resolution refinement; binding affinity; estimation of inhibitors; CGQMCTVWCSSGC targeted; conserved peptide; substitution; mimetic pharmacostructures; VEGFR-3-mediated; oncogenic effects