title: Teaching computers to fold proteins.
abstract: A new general algorithm for optimization of potential functions for protein folding is introduced. It is based upon gradient optimization of the thermodynamic stability of native folds of a training set of proteins with known structure. The iterative update rule contains two thermodynamic averages which are estimated by (generalized ensemble) Monte Carlo. We test the learning algorithm on a Lennard-Jones (LJ) force field with a torsional angle degrees-of-freedom and a single-atom side-chain. In a test with 24 peptides of known structure, none folded correctly with the initial potential functions, but two-thirds came within 3 A to their native fold after optimizing the potential functions.
authors.affiliation: Center for Biological Sequence Analysis, The Technical University of Denmark, Building 208, DK-2800 Lyngby, Denmark. owi@imm.dtu.dk
authors.forename: Ole
authors.initials: O
authors.lastname: Winther
authors.forename: Anders
authors.initials: A
authors.lastname: Krogh
mesh_terms: D000465:Algorithms; D001185:Artificial Intelligence; D003198:Computer Simulation; D008956:Models, Chemical; D008958:Models, Molecular; D015233:Models, Statistical; D011487:Protein Conformation; D017510:Protein Folding; D011506:Proteins / Q000737:chemistry*
chemical_list: D011506:Proteins