Assessing the influence of electrostatic schemes on molecular dynamics simulations of secondary structure forming peptides

Electrostatic interactions play a fundamental role in determining the
structure and dynamics of biomolecules in solution. However the accurate
representation of electrostatics in classical mechanics based simulation
approaches such as molecular dynamics (MD) is a challenging task. Given
the growing importance that MD simulation methods are taking on in the
study of protein folding, protein stability and dynamics, and in
structure prediction and design projects, it is important to evaluate
the influence that different electrostatic schemes have on the results
of MD simulations. In this paper we performed long timescale simulations
(500 ns) of two peptides, beta3 and RN24 forming different secondary
structures, using for each peptide four different electrostatic schemes
(namely PME, reaction field correction, and cut-off schemes with and
without neutralizing counterions) for a total of eight 500 ns long MD
runs. The structural and conformational features of each peptide under
the different conditions were evaluated in terms of the time dependence
of the flexibility, secondary structure evolution, hydrogen-bonding
patterns, and several other structural parameters. The degree of
sampling for each simulation as a function of the electrostatic scheme
was also critically evaluated. Our results suggest that, while in the
case of the short peptide RN24 the performances of the four methods are
comparable, PME and RF schemes perform better in maintaining the
structure close to the native one for the beta-sheet peptide beta3, in
which long range contacts are mostly responsible for the definition of
the native structure.