Molecular Dynamics Simulations of Flaviviridae Family fusion peptides

Abstract

This study comprises of conformational space explored within molecular dynamics simulations framework for flaviviridae family fusion peptides, Dengue virus serotype 2 fusion peptide (DENV2), Dengue virus serotype 3 fusion peptide (DENV3) and tick –borne encephalitis virus (TBEV) in explicit solvents at 300K with four different force fields, Amber99SB*-ILDN-Q, Charmm22/CMAP, Gromos54a7 and OPLS-AA using MD simulation techniques such as classical molecular dynamics simulations, replica exchange molecular dynamics simulations, simulated or temperature annealing that provide enhanced sampling. Experimental limitations such as failure to capture physiologically relevant time scales in order to study biological problems motivated this computational study where the protein/bimolecular dynamics can be feasibly accounted at such smaller time scales. The total simulation time was 33.6 μs. Different force fields were seen to have propensities towards different secondary structures. Amber99SB*- ILDN-Q simulations formed structures close of Dengue virus serotype 2 fusion peptide crystal structure in case of replica exchange molecular dynamics simulations method, whereas in case of methods, classic molecular dynamics simulations and temperature annealing/simulated annealing, not effective enough sampling Amber99SB*-ILDN-Q did not predict structures close to the crystal structure. Charmm22/CMAP, Gromos54a7 and OPLS-AA on the other hand were biased towards secondary structures. This study comprehends the use of sampling methods in combination with force fields in predicting structures for a small unstructured peptide that is highly dynamic in the solvent studied.