Computational Search of Evidence for the Division of Amino Acids into Transitional Groups in a Virtual State Protein. Phase I: Equilibrium Fluctuations

Abstract

Core-Shell model postulates that beyond certain resolution, non-equilibrium states are virtual, non-testable as proteinous, because they are not “domesticated” by evolution. We propose that during (un)folding, the {Cα, Cβ, Cγ, Cδ, Cɛ}-backbone of residue does an elementary move, transverse to peptide backbone. Sliding mechanism assigns amino acids into three transition groups based on residue stereochemistry. According to model, this division is masked in folded conformation. Search of evidence for such division begins with study of fluctuation of folded molecule, using united-residue protein model of sperm whale myoglobin to simulate Monte Carlo conformational trajectories. For alpha-carbon fluctuations along polypeptide chain, reasonable qualitative agreement between simulated and crystallographic B-factor (PDB ID: 108M) profiles is reached. Nearly equal amount of average rms-fluctuation contribution is found for T-groups: T1 (1.13±0.12A); T2 (1.17±0.14A); T3 (1.18±0.09A); with 1.13±0.11A being for the whole molecule. Model predicts constant-rate built-up of rms-fluctuation amounts as protein unfolds. Myoglobin has high symmetry of architecture and unusual sextet of amino acid pairs. For comparison, their rms-fluctuation amounts are: [Trp(2),Asn(2)] (1.38±0.57A); [Met(3),Tyr(3)] (0.85±0.00A); [Pro(4),Arg(4)] (1.25±0.14A); [Gln(5),Thr(5)] (1.14±0.09A); [Ser(6),Asp(6)] (1.25±0.18A); [Phe(7),Val(7)] (1.08±0.12A).View Large Image | View Hi-Res Image | Download PowerPoint Slide