METHOD OF ACQUIRING PROTEINS WITH HIGH AFFINITY BY COMPUTER AIDED DESIGN

摘要

The present invention provides a method of acquiring proteins with high affinity by computer aided design, which comprises steps of: 1) based on a known structure of a cocrystal of a complex of a protein and a target molecule, determining candidate mutation sites of the protein; 2) simulating amino acid mutations in candidate sites of the protein in turn by computer so as to acquiring optimized structures; 3) searching out conformations of optimized structures acquired in step 2) by computer; 4) analyzing total energies and root mean square deviations of conformations acquired in step 3), and then selecting conformations with minimized energy and less root mean square deviations to analyze binding energies binding to the target molecule and to acquire simulative structures; and 5) based on simulative structures acquired in step 4), predicting and validating mutated proteins with high affinity.