Method for estimating protein-protein binding affinities
View Patent ↗The present invention is directed to a method of predicting the binding affinity between a first molecular entity and a second molecular entity. The method includes (1) calculating the free energy of binding ΔG bind between the first molecular entity and the second molecular entity according to the equation (17): Δ G bind =−0.82Δ X +/− +0.064Δ X c/s −0.6 X sb −0.93 X hb −0.0007 X gap −0.06Δ X tor −0.36 (17) where X +/− is the total number of exposed charged groups; X c/s is the total number of exposed hydrophobic groups; X sb is the total number of salt bridges; X hb is the total number of hydrogen bonds; X gap is the gap volume at the interface of the first molecular entity and the second molecular entity; X tor is the total number of exposed side chain torsions; and where Δ refers to the difference between the bound and unbound states; and (2) evaluating the free energy of binding to predict the binding affinity between the first and second molecular entities.
1. A method, for execution on a computing device, of predicting the binding affinity between a first molecular entity and a second molecular entity, wherein the first molecular entity or the second molecular entity comprises a protein or a peptide, comprising the steps of:
(1) calculating the free energy of binding ΔG bind between said first molecular entity and said second molecular entity according to the following equation:
ΔG bind =−0.82 Δ X +/− +0.064Δ X c/s −0.6 X sb −0.93 X hb −0.0007 X gap −0.06Δ X tor −0.36
wherein
ΔG bind is given by a linear combination consisting of seven terms including a constant and six terms each having a coefficient and a distinct one of six parameters ΔX +/− , ΔX c/s , X sb , X hb , X gap , ΔX tor , where
X +/− is the total number of exposed charged groups;
X c/s is the total number of exposed hydrophobic groups;
X sb is the total number of salt bridges;
X hb is the total number of hydrogen bonds;
X gap is the gap volume at the interface of said first molecular entity and said second molecular entity;
X tor is the total number of exposed side chain torsions;
and wherein Δ refers to the difference between the bound and unbound states;
(2) evaluating said free energy of binding to predict the binding affinity between said first molecular entity and said second molecular entity; and
(3) outputting said evaluation to a user in a user-readable format;
wherein said calculating, said evaluating and said outputting steps are performed with the computing device, the computing device being configured to perform said steps.
2. The method of claim 1 , wherein said protein or peptide is wild type.
3. The method of claim 1 , wherein said protein or peptide is a mutant.
4. The method of claim 3 , wherein said mutant comprises one or more amino acid substitutions.
5. The method of claim 3 , wherein said mutant comprises one or more amino acid deletions.
6. The method of claim 1 wherein said second molecular entity comprises a protein or peptide.
7. The method of claim 6 , wherein said protein or peptide is wild type.
8. The method of claim 6 , wherein said protein or peptide is a mutant.
9. The method of claim 8 , wherein said mutant comprises one or more amino acid substitutions.
10. The method of claim 8 , wherein said mutant comprises one or more amino acid deletions.
11. The method of claim 1 , wherein said user-readable format is a computer display.