Molecular Dynamics of Coat Proteins of the Human Rhinovirus

Abstract

The effects of the oxazole antiviral WIN 52084 on the thermal vibrations of the coat proteins of the human rhinovirus were studied by means of a comparison of two molecular dynamics simulations. One simulation involved only a protomeric unit (cluster of four proteins) of the viral coat, while the other included the antiviral drug bound to the protein cluster. Analysis of the RMS fluctations for all atoms indicates that the drug did not cause any statistically significant global changes in the amplitude of atomic motion. However, the RMS fluctuation of seventeen residues in the vicinity of the drug decreased by about 11%. Two global effects were observed. Most importantly, the drug was found to make the decay times of the atomic fluctuations more uniform. Also, the drug lowered the average correlation time for displacements of atoms in the drug-bound cluster. Finally, a comparison of the differences in the normalized cross-correlation functions of residues close to the binding site showed that the residues move more collectively and in phase in the presence of the ligand. These results indicate that the drug has a global effect on the dynamics of the protein cluster and suggest a simple mechanical model for the action of the drug.

Key Words:

• coat proteins
• human rhinovirus
• thermal vibrations
• molecular dynamics