title: Kinetic steps for alpha-helix formation.
abstract: The kinetics of alpha-helix formation in polyalanine and polyglycine eicosamers (20-mers) were examined using torsional-coordinate molecular dynamics (MD). Of one hundred fifty-five MD experiments on extended (Ala)20 carried out for 0.5 ns each, 129 (83%) formed a persistent alpha-helix. In contrast, the extended state of (Gly)20 only formed a right-handed alpha-helix in two of the 20 MD experiments (10%), and these helices were not as long or as persistent as those of polyalanine. These simulations show helix formation to be a competition between the rates of (a) forming local hydrogen bonds (i.e. hydrogen bonds between any residue i and its i + 2, i + 3, i + 4, or i + 5th neighbor) and (b) forming nonlocal hydrogen bonds (HBs) between residues widely separated in sequence. Local HBs grow rapidly into an alpha-helix; but nonlocal HBs usually retard helix formation by "trapping" the polymer in irregular, "balled-up" structures. Most trajectories formed some nonlocal HBs, sometimes as many as eight. But, for (Ala)20, most of these eventually rearranged to form local HBs that lead to alpha-helices. A simple kinetic model describes the rate of converting nonlocal HBs into alpha-helices. Torsional-coordinate MD speeds folding by eliminating bond and angle degrees of freedom and reducing dynamical friction. Thus, the observed 210 ps half-life for helix formation is likely to be a lower bound on the real rate. However, we believe the sequential steps observed here mirror those of real systems.
authors.affiliation: Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena 91125, USA.
authors.forename: R A
authors.initials: RA
authors.lastname: Bertsch
authors.forename: N
authors.initials: N
authors.lastname: Vaidehi
authors.forename: S I
authors.initials: SI
authors.lastname: Chan
authors.forename: W A
authors.initials: WA
authors.lastname: Goddard
mesh_terms: D003198:Computer Simulation; D006860:Hydrogen Bonding; D007700:Kinetics; D008958:Models, Molecular; D010455:Peptides / Q000737:chemistry*; D017433:Protein Structure, Secondary
chemical_list: D010455:Peptides; C019529:polyalanine; C011080:polyglycine