In Silico Induction of Missense Mutation in NNRTI Protein: Computational Modelling Studies on Design of Modelled Proteins and their Stability Studies.

Abstract

Abstract The work presents in silico mutational studies on the energetics of HIV-1 reverse transcriptase protein 4G1Q, the highest resolved protein structure of NNRTIs of HIV-1. In silico mutations are induced on the twenty neighbouring residues, surrounding the embedded ligand, within the vicinity of 6 Å from the centre of the ligand. These 20 surrounding residues are mutated and a set of 380 novel proteins are designed in silico for the present study. The effects of mutation on the change in folding-unfolding free energy (ΔΔG), protein stability and solvation energy have been analysed and compared with the parent protein. A two-fold study is performed to assess the effect of mutation (i) by and (ii) on a specific amino acid residue. The results suggest that folding-unfolding is highly favoured in 12 designed proteins (ΔΔG < -3.0) leading to the formation of highly stable conformation. In 11 designed proteins the positive values of ΔΔG > 0.5, suggest unfavourable mutations, thus the resultant designed proteins are unstable. Though, in 171 designed proteins the ΔΔG is <-1.0 suggesting the results suggest mutations lead to the stable conformation of designed proteins. The results suggest that of all the 380 designed proteins 11 showed highly unfavourable, 69 less favourable and 270 showed favourable folding-unfolding transformations.