Evaluating and optimizing computational protein design force fields using fixed composition-based negative design.

ABSTRACT: An accurate force field is essential to computational protein design and protein fold prediction studies. Proper force field tuning is problematic, however, due in part to the incomplete modeling of the unfolded state. Here, we evaluate and optimize a protein design force field by constraining the amino acid composition of the designed sequences to that of a well behaved model protein. According to the random energy model, unfolded state energies are dependent only on amino acid composition and not the specific arrangement of amino acids. Therefore, energy discrepancies between computational predictions and experimental results, for sequences of identical composition, can be directly attributed to flaws in the force field's ability to properly account for folded state sequence energies. Th

SUBMITTER: Alvizo O 

PROVIDER: S-EPMC2516967 | biostudies-literature | 2008 Aug

REPOSITORIES: biostudies-literature