Computational binding studies of human pp60c-src SH2 domain with a series of nonpeptide, phosphophenyl-containing ligands

Bioorg Med Chem Lett. 2000 Sep 18;10(18):2067-70. doi: 10.1016/s0960-894x(00)00401-7.

Abstract

Monte Carlo/free energy perturbation (MC/FEP) simulations were performed on a series of nonpeptide ligands of the human pp60c-src SH2 domain in order to calculate relative free energies of binding for each compound and to understand the structural requirements for high affinity binding. The amido compound, exhibiting the highest experimental affinity, takes advantage of an interaction with a previously unobserved structural water.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Binding Sites
  • Humans
  • Ligands
  • Models, Chemical
  • Molecular Conformation
  • Monte Carlo Method
  • Organophosphates / chemistry
  • Organophosphates / metabolism
  • Protein Binding
  • Proto-Oncogene Proteins pp60(c-src) / chemistry*
  • Proto-Oncogene Proteins pp60(c-src) / metabolism
  • Structure-Activity Relationship
  • Thermodynamics
  • src Homology Domains*

Substances

  • Ligands
  • Organophosphates
  • phenylphosphate
  • Proto-Oncogene Proteins pp60(c-src)

Associated data

  • PDB/1HCS
  • PDB/1SHD