Abstract
In this study, we had exploited the advancement in computer technology to determine the stability of four apomyoglobin variants namely wild type, E109A, E109G and G65A/G73A by conducting conventional molecular dynamics simulations in explicit urea solution. Variations in RMSD, native contacts and solvent accessible surface area of the apomyoglobin variants during the simulation were calculated to probe the effect of mutation on the overall conformation of the protein. Subsequently, the mechanism leading to the destabilization of the apoMb variants was studied through the calculation of correlation matrix, principal component analyses, hydrogen bond analyses and RMSF. The results obtained here correlate well with the study conducted by Baldwin and Luo which showed improved stability of apomyoglobin with E109A mutation and contrariwise for E109G and G65A/G73A mutation. These positive observations showcase the feasibility of exploiting MD simulation in determining protein stability prior to protein expression.
Highlights
Over the last few decades, researches involving proteins have extended beyond the scope of solely exploring the relationship between proteins’ structure and function to one that involves altering the structures and functions of protein biomolecules for beneficial use in biotechnological innovations in both laboratory and industrial application[1,2,3,4,5,6]
The stability pattern determined through this theoretical work will be compared with the stability ranking of apoMb variants determined by Luo et al who studied the role of helix propensity on the stability of six apoMb mutants namely E109A, E109G, Q8A, Q8G, G23A/G25A and G65A/G73A using reversible urea unfolding observed through circular dichroism (CD) and fluorescence (FL)[9]
The stability of eight apoMb variants viz. wild type, E109A, E109G, Q8A, Q8G, K140A, G23A/G25A and G65A/ G73A had been explored by Luo et al experimentally through reversible urea unfolding of these proteins which were monitored through CD and FL9
Summary
Over the last few decades, researches involving proteins have extended beyond the scope of solely exploring the relationship between proteins’ structure and function to one that involves altering the structures and functions of protein biomolecules for beneficial use in biotechnological innovations in both laboratory and industrial application[1,2,3,4,5,6]. Theoretical studies utilizing MD simulation empowered in-depth observation of the intricate dynamics of biological macromolecules permitting the understanding of protein folding and unfolding, protein stability and conformational changes[11] These interesting applications offered by MD simulation are useful in designing proteins as it allows one to provide insights on the feasibility of the mutation performed in maintaining the overall conformation of the native protein while simultaneously providing information regarding crucial interactions (e.g. hydrophobic interactions, Van der Waals, hydrogen bond) that may govern the stability of the studied protein. The stability pattern determined through this theoretical work will be compared with the stability ranking of apoMb variants determined by Luo et al who studied the role of helix propensity on the stability of six apoMb mutants namely E109A, E109G, Q8A, Q8G, G23A/G25A and G65A/G73A using reversible urea unfolding observed through circular dichroism (CD) and fluorescence (FL)[9]
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