Evaluating the Impact of Conformational Dynamics on Predicted Protein Protonation State: A Case Study on Brome Mosaic Virus

Researcher(s)

  • Anoushka Buddhikot, Chemical Engineering, University of Delaware

Faculty Mentor(s)

  • Jodi Hadden-Perilla, Chemistry and Biochemistry, University of Delaware

Abstract

Brome Mosaic Virus (BMV) is a small plant virus with an icosahedral capsid structure. The BMV capsid is a repeating pattern of three quasi-equivalent protein chains (A, B, and C), which have the same amino acid sequence but different conformations. Previous experimental studies have shown that the BMV capsid expands under high pH conditions. Atomistic molecular dynamics simulations are used to model the BMV capsid in a buffer solution mimicking various pH environments, including one that induces swelling. A current limitation of classical molecular dynamics simulations is that the protonation state of each amino acid is determined for the initial conformation and maintained throughout the simulation. However, as the protein undergoes conformational changes, the local environment of these amino acids can change such that the initial prediction for the protonation state is no longer accurate. Here, the individual A, B, and C chains of the BMV capsid are simulated under pH conditions ranging from 4.5 to 8 and the accuracy of the protonation state prediction for the initial state is assessed for titratable residues throughout the simulation. Similar analysis is conducted on trajectory data from a simulation of the full BMV capsid. The results of this analysis will inform more complex and more accurate simulations of BMV and other icosahedral viruses.