title: Beta-sheet containment by flanking prolines: molecular dynamic simulations of the inhibition of beta-sheet elongation by proline residues in human prion protein.
abstract: Previous molecular dynamic simulations have reported elongation of the existing beta-sheet in prion proteins. Detailed examination has shown that these elongations do not extend beyond the proline residues flanking these beta-sheets. In addition, proline has also been suggested to possess a possible structural role in preserving protein interaction sites by preventing invasion of neighboring secondary structures. In this work, we have studied the possible structural role of the flanking proline residues by simulating mutant structures with alternate substitution of the proline residues with valine. Simulations showed a directional inhibition of elongation, with the elongation progressing in the direction of valine including evident inhibition of elongation by existing proline residues. This suggests that the flanking proline residues in prion proteins may have a containment role and would confine the beta-sheet within a specific length.
authors.affiliation: Biology Department, Faculty of Science, Universiti Teknologi Malaysia, 81310 Skudai, Johor.
authors.forename: Mohd S
authors.initials: MS
authors.lastname: Shamsir
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Dalby
mesh_terms: D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry* / Q000648:ultrastructure*; D003198:Computer Simulation; D007700:Kinetics; D008565:Membrane Proteins / Q000737:chemistry* / Q000648:ultrastructure*; D000072236:Methyl-Accepting Chemotaxis Proteins; D008956:Models, Chemical; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009038:Motion; D011328:Prions / Q000737:chemistry* / Q000648:ultrastructure*; D011392:Proline / Q000737:chemistry*; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D013223:Statistics as Topic; D013329:Structure-Activity Relationship
chemical_list: D001426:Bacterial Proteins; D008565:Membrane Proteins; D000072236:Methyl-Accepting Chemotaxis Proteins; D011328:Prions; D011392:Proline