Computer simulations of the properties of the alpha(2), and alpha C-2 and alpha D-2 de novo designed helical proteins

Reduced lattice models of the three de novo designed helical proteins alpha (2), alpha(2)C, and alpha(2)D were studied. Low temperature stable folds we re obtained for all three proteins. In all cases, the lowest energy folds w ere four-helix bundles. The folding pathway is qualitatively the same for a ll proteins studied. The energies of various topologies are similar, especi ally for the alpha(2) polypeptide. The simulated crossover from molten glob ule to nativelike behavior is very similar to that seen in experimental stu dies. Simulations on a reduced protein model reproduce most of the experime ntal properties of the alpha(2), alpha(2)C, and alpha(2)D proteins. Stable four-helix bundle structures were obtained, with increasing native-like beh avior on-going from alpha(2) to alpha(2)D that mimics experiment. Proteins 2000; 38:17-28, (C) 2000 Wiley-Liss, Inc.