Directed protein docking algorithm

An apparatus for redesigning a candidate polypeptide sequence to alter interaction with a target biopolymer, said apparatus comprising:

• (a) means for providing (i) an atomic coordinate model of a candidate polypeptide having a reference amino acid sequence, which model includes coordinates for backbone atoms and coordinates for no more than Cβ atoms of amino acid side-chains of said reference amino acid sequence, and (ii) an atomic coordinate model for at least a docking surface of said target biopolymer;
• (b) means for identifying, by surface-to-surface geometric fitting, a model of a complex between said target biopolymer model and said candidate polypeptide model that has at least a predefined degree of surface shape complementarity;
• (c) means for identifying amino acid residues in said candidate polypeptide with unfavorable interactions with said target biopolymer in said complex as varying residues;
• (d) means for generating one or more model(s) of said complex in which said candidate polypeptide model includes atomic coordinates of more than the Cβ atoms of said varying residue side-chains, and identifying mutations of said varying residues that form more favorable interactions with said target biopolymer model.

A computer system for use in redesigning a candidate polypeptide sequence to alter interaction with a target biopolymer, said computer system comprising computer instructions for:

• (a) providing (i) an atomic coordinate model of a candidate polypeptide having a reference amino acid sequence, which model includes coordinates for backbone atoms and coordinates for no more than Cβ atoms of amino acid side-chains of said reference amino acid sequence, and (ii) an atomic coordinate model for at least a docking surface of said target biopolymer;
• (b) identifying, by surface-to-surface geometric fitting, a model of a complex between said target biopolymer model and said candidate polypeptide model that has at least a predefined degree of surface shape complementarity;
• (c) identifying amino acid residues in said candidate polypeptide with unfavorable interactions with said target biopolymer in said complex as varying residues;
• (d) generating one or more model(s) of said complex in which said candidate polypeptide model includes atomic coordinates of more than the Cβ atoms of said varying residue side-chains, and identifying mutations of said varying residues that form more favorable interactions with said target biopolymer model.

A computer-readable medium storing a computer program executable by a plurality of server computers, the computer program comprising computer instructions for:

• (a) providing (i) an atomic coordinate model of a candidate polypeptide having a reference amino acid sequence, which model includes coordinates for backbone atoms and coordinates for no more than Cβ atoms of amino acid side-chains of said reference amino acid sequence, and (ii) an atomic coordinate model for at least a docking surface of said target biopolymer;
• (b) identifying, by surface-to-surface geometric fitting, a model of a complex between said target biopolymer model and said candidate polypeptide model that has at least a predefined degree of surface shape complementarity;
• (c) identifying amino acid residues in said candidate polypeptide with unfavorable interactions with said target biopolymer in said complex as varying residues;
• (d) generating one or more model(s) of said complex in which said candidate polypeptide model includes atomic coordinates of more than the Cβ atoms of said varying residue side-chains, and identifying mutations of said varying residues that form more favorable interactions with said target biopolymer model.

A computer data signal embodied in a carrier wave, comprising computer instructions for:

• (a) providing (i) an atomic coordinate model of a candidate polypeptide having a reference amino acid sequence, which model includes coordinates for backbone atoms and coordinates for no more than Cβ atoms of amino acid side-chains of said reference amino acid sequence, and (ii) an atomic coordinate model for at least a docking surface of said target biopolymer;
• (b) identifying, by surface-to-surface geometric fitting, a model of a complex between said target biopolymer model and said candidate polypeptide model that has at least a predefined degree of surface shape complementarity;
• (c) identifying amino acid residues in said candidate polypeptide with unfavorable interactions with said target biopolymer in said complex as varying residues;
• (d) generating one or more model(s) of said complex in which said candidate polypeptide model includes atomic coordinates of more than the Cβ atoms of said varying residue side-chains, and identifying mutations of said varying residues that form more favorable interactions with said target biopolymer model.

An apparatus comprising a computer readable storage medium having instructions stored thereon for:

• (a) accessing a datafile representative of (i) an atomic coordinate model of a candidate polypeptide having a reference amino acid sequence, which model includes coordinates for backbone atoms and coordinates for no more than Cβ atoms of amino acid side-chains of said reference amino acid sequence, and (ii) an atomic coordinate model for at least a docking surface of said target biopolymer;
• (b) accessing a datafile representative of the atomic coordinates for a plurality of different rotamers of amino acids resulting from varying torsional angles;
• (c) a set of modeling routines for:
• (1) identifying surface-to-surface geometric fitting by docking said candidate polypeptide and said target biopolymer to form a complex with a predefined degree of surface shape complementarity between said candidate polypeptide and said target biopolymer;
• (2) generating one or more model(s) of said complex in which said candidate polypeptide model includes atomic coordinates of more than the Cβ atoms of said varying residue side-chains, and identifying mutations of said varying residues that form more favorable interactions with said target biopolymer model.