ISSN:
0887-3585
Schlagwort(e):
α-helix
;
polyalanine
;
polyglutamine
;
folding
;
NEIMO
;
Chemistry
;
Biochemistry and Biotechnology
Quelle:
Wiley InterScience Backfile Collection 1832-2000
Thema:
Medizin
Notizen:
The kinetics of α-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 α-helix. In contrast, the extended state of (Gly)20 only formed a right-handed α-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 α-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 α-helices. A simple kinetic model describes the rate of converting nonlocal HBs into α-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. Proteins 33:343-357, 1998. © 1998 Wiley-Liss, Inc.
Zusätzliches Material:
13 Ill.
Materialart:
Digitale Medien
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