Peptide docking using dynamic programming

Abstract

An extended dynamic programming algorithm is presented that is applicable to the fragment assembly phase of the site mapping fragment assembly approach to peptide docking. After constructing a free energy map of the receptor using each of the amino acids in the peptides to be docked, we apply the algorithm to two systems: HIV-1 protease complexed with a synthetic hexameric inhibitor, and MHC HLA-A2 complexed with a nonameric peptide. The all atom root mean square deviation between the predicted and crystal structures was 1.7 and 2.0 Å, respectively. While these results are reasonable considering the relatively coarse level of mapping, the more important result is that the structures are probably very close to the best obtainable by an exhaustive search through the entire data map, and yet are obtained with a reduction of 3–5 orders of magnitude in the number of computations. We also outline a prescription for an iterative procedure which finds the global minimum with increasing confidence. © 1996 by John Wiley & Sons, Inc.