Molecular dynamics simulation of equine infectious anemia virus Tat protein in water and in 40% trifluoroethanol.

This research represents a study about the impact of solvent environments on protein shape using molecular dynamics simulations. The specific protein looked at was the activator for the equine infectious anemia virus and the solvent environments included water and 40% trifluoroethanol.

Overview of the Research

• The study aims to better understand how protein shape or conformation depends on various solvent environments. This was targeted using molecular dynamics (MD) simulations to model the behavior of the equine infectious anemia virus’s transcriptional activator (EIAV-Tat) in water and a 40% trifluoroethanol (TFE) solvent environment.
• The structure of the EIAV-Tat protein had been previously determined by nuclear magnetic resonance (NMR) in water as well as in 40% TFE. It was found that there were significant differences in the stability of secondary structure elements in each of these environments.

Methodology And Findings

• For better investigating the influence of the solvent, MD simulations of 200 picoseconds at 300 Kelvin were conducted for each environment, using the protein structure as observed in 40% TFE as the initial structure.
• The simulations showed decreased stability of the secondary structure elements in water, as can be seen by larger atomic motions and stronger fluctuation in hydrogen bond lengths. This was however not observed to lead to complete unfolding of the helices within the 200 picosecond timeframe of the study.
• The root mean square deviation (RMSD) of the backbone atoms from the starting structure after the 200 picosecond simulation was 1.95 angstroms for the water environment and 1.29 angstroms for the TFE/water mix. RMSD is a measure of similarity between two superimposed sets of points, and denotes the average distance between the atoms (commonly the backbone atoms of superimposed proteins) of the two structures.

Conclusion and Implication

• The results suggested a strong influence of the solvent environment on the protein’s stability, and supported the idea that TFE can act to induce and stabilize secondary structure.
• Interestingly, the differences noticed in the MD simulations align well with data derived from NMR measurements, affirming the utility of MD as a method to potentially predict the conformational and dynamical properties of proteins.