Combinatorial methods for small-molecule placement in computational enzyme design.

ABSTRACT: The incorporation of small-molecule transition state structures into protein design calculations poses special challenges because of the need to represent the added translational, rotational, and conformational freedoms within an already difficult optimization problem. Successful approaches to computational enzyme design have focused on catalytic side-chain contacts to guide placement of small molecules in active sites. We describe a process for modeling small molecules in enzyme design calculations that extends previously described methods, allowing favorable small-molecule positions and conformations to be explored simultaneously with sequence optimization. Because all current computational enzyme design methods rely heavily on sampling of possible active site geometries from discrete co

SUBMITTER: Lassila JK 

PROVIDER: S-EPMC1636520 | biostudies-literature | 2006 Nov

REPOSITORIES: biostudies-literature