A Novel Method for Enzyme Design

【作者】 祝小雷； 来鲁华；

【Author】 Xiaolei Zhu Luhua Lai Beijing National Laboratory for Molecular Sciences,State Key Laboratory for Structural Chemistry of Unstable and Stable Species,College of Chemistry and Molecular Engineering,Peking University,Beijing 100871,China.& Center for Theoretical Biology,Peking University,Beijing 100871,China

【机构】 Beijing National Laboratory for Molecular Sciences,State Key Laboratory for Structural Chemistry of Unstable and Stable Species,College of Chemistry and Molecular Engineering,Peking University； Center for Theoretical Biology,Peking University；

【摘要】 <正>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.更多还原

【Abstract】 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.更多还原