title: De novo Folding of Two-Helix Potassium Channel Blockers with Free-Energy Models and Molecular Dynamics.
abstract: We report the predictive de novo folding of three two-helix proteins using the free-energy protein forcefield PFF01. Starting from random initial conformations 40-90% of the members of the simulated ensembles converge to near-native conformations. The energetically lowest conformations approach the conserved part of the native conformations to within 1.64, 1.86, and 1.84 Å for 1WQC, 1WQD, and 1WQE, respectively. An analysis of the low-lying conformations predicts the correct topology of the disulfide bridges, which are formed in additional simulations with a constraining potential. The free energy landscapes of these proteins are very simple, suggesting them as candidates for all-atom molecular dynamics simulations. In five independent simulations we find the formation of the correct secondary structure and several folding events into the tertiary structure.
authors.affiliation: Forschungszentrum Karlsruhe, Institute für Nanotechnologie, P.O. Box 3640, 76021 Karlsruhe, Germany.
authors.forename: Aina
authors.initials: A
authors.lastname: Quintilla
authors.affiliation: Forschungszentrum Karlsruhe, Institute für Nanotechnologie, P.O. Box 3640, 76021 Karlsruhe, Germany.
authors.forename: Evgeni
authors.initials: E
authors.lastname: Starikov
authors.affiliation: Forschungszentrum Karlsruhe, Institute für Nanotechnologie, P.O. Box 3640, 76021 Karlsruhe, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Wenzel