论文部分内容阅读
Rational design of enzymes is a stringent test of our understanding of protein structure and function relationship which also has numerous potential applications.We present a novel method for enzyme design that can find good candidate protein scaffolds in a protein-ligand database based on vector matching of key residues.Residues in the vicinity of the active site were also compared according to a similarity score between the scaffold protein and the target enzyme.Suitable scaffold proteins were selected and the side chains of residues around the active sites were rebuilt using a previously developed side chain packing program.Triose phosphate isomerase (TIM) was used as a validation test for enzyme design.Selected scaffold proteins were found to accommodate the enzyme active sites and successfully form a good transition state complex.This method overcomes the limitations of the current enzyme design methods that use limited number of protein scaffold and based on the position of ligands.As there is a large number of protein scaffolds available in the Protein Data Band, this method should be widely applicable for various types of enzyme design.