Apparatus and method for automated protein design

Abstract

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

1 . 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 with a plurality of variable residue positions;    b) computationally generating a first 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 at least one variant residue position; and    c) computationally generating a second set of suboptimal variant sequences from said set.    
     
     
         2 . A method according to  claim 1  wherein said first set comprises the global minimum using said scoring function.  
     
     
         3 . A method according to  claim 1  wherein said first set consists of the global minimum using said scoring function.  
     
     
         4 . A method according to  claim 1  wherein said second set is generated using a Monte Carlo search.  
     
     
         5 . A method according to  claim 1  wherein said variable residue positions are classified as core, surface or boundary residues.  
     
     
         6 . A method according to  claim 1  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.  
     
     
         7 . A method according to  claim 1  wherein said computational generation of said first set utilizes at least two scoring functions.  
     
     
         8 . A method according to  claim 1  wherein said computational generation of said first set utilizes at least three scoring functions.  
     
     
         9 . A method according to  claim 1  wherein said computational generation of said first set utilizes at least four scoring functions.