Prediction of the mutation-induced change in thermodynamic stabilities of membrane proteins from free energy simulations.
Comparative protein structure modeling and free energy perturbation simulation have been applied in a consecutive manner to investigate the mutation-induced stabilization of membrane proteins (MPs) in aqueous solution without knowledge of their three-dimensional structures. The calculated difference in protein solvation free energy between the wild type and a mutant compares well with their relative thermodynamic stabilities in solution. For monomeric MPs, a mutant reveals a higher stability than the wild type if the calculated solvation free energy indicates a favorable change. On the contrary, for oligomeric MPs the stability of a mutant increases as the solvation free energy of a mutated monomer becomes less favorable, indicating that the oligomeric MP mutant would be stabilized in solution due to the reduced desolvation cost for oligomerization. The present computational strategy is expected to find its way as a useful tool for assessing the relative stability of a mutant MP with respect to its wild type in solution.
Park
Hwangseo
H
School of Chemistry and Molecular Engineering, Seoul National University, Korea.
Lee
Sangyoub
S
D000595:Amino Acid Sequence; D001436:Bacteriorhodopsins / Q000737:chemistry; D036022:Capsid Proteins / Q000737:chemistry; D003198:Computer Simulation; D008565:Membrane Proteins / Q000737:chemistry* / Q000235:genetics; D026901:Membrane Transport Proteins / Q000737:chemistry; D008969:Molecular Sequence Data; D017354:Point Mutation; D018272:Porins / Q000737:chemistry; D011487:Protein Conformation; D011489:Protein Denaturation; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D040681:Structural Homology, Protein; D013816:Thermodynamics
D036022:Capsid Proteins; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; C109237:OmpF protein; D018272:Porins; C025668:coat protein, Bacteriophage M13; D001436:Bacteriorhodopsins; C021499:lactose permease