Abstract:
        We propose an alternative stochastic strategy to search secondary structures based on the generalized simulated annealing (GSA) algorithm, by using conformational preferences based on the Ramachandran map. We optimize the search for polypeptide conformational space and apply to peptides considered to be good alpha-helix promoters above a critical number of residues. Our strategy to obtain conformational energies consist in coupling a classical force field (THOR package) with the GSA procedure, biasing the Phi x Psi backbone angles to the allowed regions in the Ramachandran map. For polyalanines we obtained stable alpha-helix structures when the number of residues were equal or exceeded 13 amino acids residues. We also observed that the energy gap between the global minimum and the first local minimum tends to increase with the polypeptide size. These conformations were generated by performing 2880 stochastic molecular optimizations with a continuum medium approach. When compared with molecular dynamics or Monte Carlo methods, GSA can be considered the fastest.

KeyWords Plus:
MOLECULAR-DYNAMICS SIMULATION, ALANINE-BASED PEPTIDES, COIL TRANSITION, ALPHA-HELICES, OPTIMIZATION, STABILITY, KINETICS, PATHWAYS, MODEL, WATER

Addresses:
Bisch PM, Univ Fed Rio de Janeiro, Inst Biofis, CCS, Bloco G Ilha Fundao, BR-21919900 Rio De Janeiro, Brazil
Univ Fed Rio de Janeiro, Inst Biofis Carlos Chagas Filho, BR-21919900 Rio De Janeiro, Brazil
Univ Estadual Feira de Santana, Dept Fis, Feira De Santana, Brazil
Univ Brasilia, Inst Quim, Brasilia, DF, Brazil

Publisher: BIOPHYSICAL SOCIETY, BETHESDA

ISSN: 0006-3495