Patent ID: 6385546
Filing Date: 2002-05-07
Classification: G16B

Abstract:
A method of designing a variant of a selected wild-type protein that is a candidate for having increased thermophilicity compared to the wild-type protein, comprising:a) providing the atomic coordinates of the selected wild-type protein in its folded conformation; b) using the atomic coordinates to calculate a first solvent accessible surface area for each polar charged atom of the selected wild-type protein when the selected wild-type protein is in its folded conformation; c) calculating a first sum, the first sum being the sum of the first solvent accessible surface areas of the polar charged atoms for an amino acid having a formal charge wherein the amino acid is outside of an active site of the selected wild-type protein and does not interact with an active site of the selected wild-type protein; d) calculating a second solvent accessible surface area for each polar charged atom in the selected wild-type protein when the protein is in an extended conformation; e) calculating a second sum, the second sum being the sum of the second solvent accessible surface areas of the polar charged atoms for the amino acid having a formal charge; f) determining that the amino acid having a formal charge is at least partially buried when the first sum is less than the second sum by at least 29%; and g) designing a variant protein that is a candidate for having increased thermophilicity compared to the wild-type protein by replacing one or more at least partially buried amino acids with an amino acid having no formal charge.