Protein-ligand docking using FFT based sampling: D3R case study

J Comput Aided Mol Des. 2018 Jan;32(1):225-230. doi: 10.1007/s10822-017-0069-7. Epub 2017 Nov 3.

Abstract

Fast Fourier transform (FFT) based approaches have been successful in application to modeling of relatively rigid protein-protein complexes. Recently, we have been able to adapt the FFT methodology to treatment of flexible protein-peptide interactions. Here, we report our latest attempt to expand the capabilities of the FFT approach to treatment of flexible protein-ligand interactions in application to the D3R PL-2016-1 challenge. Based on the D3R assessment, our FFT approach in conjunction with Monte Carlo minimization off-grid refinement was among the top performing methods in the challenge. The potential advantage of our method is its ability to globally sample the protein-ligand interaction landscape, which will be explored in further applications.

Keywords: D3R; Drug design data resource; FFT sampling; Protein ligand docking.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • 17-alpha-Hydroxyprogesterone / chemistry
  • 17-alpha-Hydroxyprogesterone / pharmacology*
  • Binding Sites
  • Calcifediol / chemistry
  • Calcifediol / pharmacology*
  • Computer-Aided Design
  • Drug Design
  • Fourier Analysis*
  • Humans
  • Ligands
  • Molecular Docking Simulation*
  • Monte Carlo Method
  • Protein Binding
  • Proteins / chemistry
  • Proteins / metabolism*

Substances

  • Ligands
  • Proteins
  • 17-alpha-Hydroxyprogesterone
  • Calcifediol