Apparatus and method for automated protein design

Abstract

The present invention relates to apparatus and methods for quantitative protein design and optimization.

1 - 29 . (canceled)  
     
     
         30 . A method executed by a computer under the control of a program, said computer including a memory for storing said program, said method comprising the steps of: 
 a) receiving a set of three dimensional coordinates for a target protein having a protein backbone structure and a plurality of variable residue positions;    b) altering the coordinates of a plurality of atoms of said backbone structure of said target protein; and    c) computationally generating a set of rank ordered optimized variant sequences using at least one scoring function, wherein said variant sequences comprise at least one variant amino acid at least one variant residue position.    
     
     
         31 . The method according to  claim 30  wherein said set comprises the global minimum using said scoring function.  
     
     
         32 . The method according to  claim 30  wherein said set consists of the global minimum using said scoring function.  
     
     
         33 . The method according to  claim 30  wherein said variable residue positions are classified as core, surface or boundary residues.  
     
     
         34 . The method according to  claim 30  wherein said scoring function is selected from the group consisting of a van der Waals potential scoring function, a hydrogen bond potential scoring function, an atomic solvation scoring function, an electrostatic scoring function and a secondary structure propensity scoring function.  
     
     
         35 . The method according to  claim 30  wherein said computational generation of said set utilizes at least two scoring functions.  
     
     
         36 . The method according to  claim 30  wherein said computational generation of said set utilizes at least three scoring functions.  
     
     
         37 . The method according to  claim 30  wherein said computational generation of said set utilizes at least four scoring functions.  
     
     
         38 . The method of  claim 30  wherein said altering is by altering at least one supersecondary structure parameter of said backbone structure.  
     
     
         39 . A computer readable memory that upon execution by a computer processor performs the method of  claim 30 .  
     
     
         40 . The computer readable memory according to  claim 39  wherein said set comprises the global minimum using said scoring function.  
     
     
         41 . The computer readable memory according to  claim 39  wherein said set consists of the global minimum using said scoring function.  
     
     
         42 . The computer readable memory according to  claim 39  wherein said variable residue positions are classified as core, surface or boundary residues.  
     
     
         43 . The computer readable memory according to  claim 39  wherein said scoring function is selected from the group consisting of a van der Waals potential scoring function, a hydrogen bond potential scoring function, an atomic solvation scoring function, an electrostatic scoring function and a secondary structure propensity scoring function.  
     
     
         42 . The computer readable memory according to  claim 39  wherein said computational generation of said set utilizes at least two scoring functions.  
     
     
         43 . The computer readable memory according to  claim 39  wherein said computational generation of said set utilizes at least three scoring functions.  
     
     
         44 . The computer readable memory according to  claim 39  wherein said computational generation of said set utilizes at least four scoring functions.  
     
     
         45 . The computer readable memory of  claim 39 , wherein said altering is by altering at least one super secondary structure parameter of said backbone structure.  
     
     
         46 . A computer processor that executes the computer readable memory of  claim 39.