title: Accounting for a mirror-image conformation as a subtle effect in protein folding.
abstract: By using local (free-energy profiles along the amino acid sequence and (13)C(α) chemical shifts) and global (principal component) analyses to examine the molecular dynamics of protein-folding trajectories, generated with the coarse-grained united-residue force field, for the B domain of staphylococcal protein A, we are able to (i) provide the main reason for formation of the mirror-image conformation of this protein, namely, a slow formation of the second loop and part of the third helix (Asp29-Asn35), caused by the presence of multiple local conformational states in this portion of the protein; (ii) show that formation of the mirror-image topology is a subtle effect resulting from local interactions; (iii) provide a mechanism for how protein A overcomes the barrier between the metastable mirror-image state and the native state; and (iv) offer a plausible reason to explain why protein A does not remain in the metastable mirror-image state even though the mirror-image and native conformations are at least energetically compatible.
authors.affiliation: Baker Laboratory of Chemistry and Chemical Biology, Cornell University, Ithaca, NY 14853-1301;
authors.forename: Khatuna
authors.initials: K
authors.lastname: Kachlishvili
authors.affiliation: Baker Laboratory of Chemistry and Chemical Biology, Cornell University, Ithaca, NY 14853-1301;
authors.forename: Gia G
authors.initials: GG
authors.lastname: Maisuradze
authors.affiliation: Baker Laboratory of Chemistry and Chemical Biology, Cornell University, Ithaca, NY 14853-1301;Instituto de Matemática Aplicada San Luis, Consejo Nacional de Investigaciones Científicas y Técnicas de Argentina, Universidad Nacional de San Luis, 5700 San Luis, Argentina; and.
authors.forename: Osvaldo A
authors.initials: OA
authors.lastname: Martin
authors.affiliation: Laboratory of Molecular Modeling, Faculty of Chemistry, University of Gdańsk, 80-308 Gdańsk, Poland.
authors.forename: Adam
authors.initials: A
authors.lastname: Liwo
authors.affiliation: Baker Laboratory of Chemistry and Chemical Biology, Cornell University, Ithaca, NY 14853-1301;Instituto de Matemática Aplicada San Luis, Consejo Nacional de Investigaciones Científicas y Técnicas de Argentina, Universidad Nacional de San Luis, 5700 San Luis, Argentina; and.
authors.forename: Jorge A
authors.initials: JA
authors.lastname: Vila
authors.affiliation: Baker Laboratory of Chemistry and Chemical Biology, Cornell University, Ithaca, NY 14853-1301; has5@cornell.edu.
authors.forename: Harold A
authors.initials: HA
authors.lastname: Scheraga
mesh_terms: D000465:Algorithms; D000595:Amino Acid Sequence; D007700:Kinetics; D008956:Models, Chemical; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D008969:Molecular Sequence Data; D025341:Principal Component Analysis; D011487:Protein Conformation; D017510:Protein Folding; D017433:Protein Structure, Secondary; D011506:Proteins / Q000737:chemistry*; D013205:Staphylococcal Protein A / Q000737:chemistry; D013816:Thermodynamics; D013997:Time Factors
chemical_list: D011506:Proteins; D013205:Staphylococcal Protein A
keywords: misfolding; symmetrical proteins