title: Application of conventional molecular dynamics simulation in evaluating the stability of apomyoglobin in urea solution.
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.
authors.affiliation: School of Physics and Engineering, Henan University of Science and Technology, Luoyang 471023, P. R. China.
authors.forename: Dawei
authors.initials: D
authors.lastname: Zhang
authors.affiliation: Division of Chemistry and Biological Chemistry, School of Physical and Mathematical Sciences, Nanyang Technological University, Singapore 637371, Singapore.
authors.forename: Raudah
authors.initials: R
authors.lastname: Lazim
mesh_terms: D000818:Animals; D001059:Apoproteins / Q000737:chemistry* / Q000235:genetics; D002942:Circular Dichroism; D015870:Gene Expression / Q000235:genetics; D006860:Hydrogen Bonding; D056004:Molecular Dynamics Simulation; D009211:Myoglobin / Q000737:chemistry* / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011487:Protein Conformation; D011489:Protein Denaturation; D017510:Protein Folding; D055550:Protein Stability / Q000187:drug effects*; D012996:Solutions / Q000737:chemistry* / Q000633:toxicity; D012997:Solvents / Q000737:chemistry; D050661:Sperm Whale; D013329:Structure-Activity Relationship; D014508:Urea / Q000633:toxicity
chemical_list: D001059:Apoproteins; D009211:Myoglobin; D012996:Solutions; D012997:Solvents; C010857:apomyoglobin; D014508:Urea