Characterisation of the effect of electrostatic interaction on the structure of Trp-cage using molecular dynamics simulation

Abstract

A mutated variant of 20 amino acid miniprotein Trp-cage (TC5b), called TC5c (Asp9 replaced by Asn9), was designed to demonstrate the effect of a salt bridge. As a result of strong electrostatic interaction, the distance distribution between Asp9 and Arg16 exhibited a larger probability in the range of the salt bridge for TC5b compared to TC5c. The probability of α-helix formation for residues 3–8, as well as for residues 11–14, was high for TC5b. The salt bridge formation between Asp9 and Arg16 in TC5b was indicated by (a) a strong correlation of their distance of separation with the subtended angle with the centre and (b) a step decrease in the distance between Gly11O and Arg16H at 12 ns. Replica exchange molecular dynamics simulation at different temperatures in the range of 270–590 K indicated that the average distance between Asp9 and Arg16, end-to-end distance, root mean square deviation with respect to a reference NMR structure of TC5b did not change significantly with temperature below 370 K for TC5b and increased at higher temperatures. These values were higher for TC5c for the whole temperature range, with their rate of increase with temperature being higher below 370 K.

Keywords:

• Trp-cage
• molecular dynamics
• AMBER
• protein folding
• salt bridge

Acknowledgements

We would like to acknowledge the Purdue Research Foundation for providing financial support to X.W.