Format

Send to

Choose Destination
See comment in PubMed Commons below
J Chem Inf Model. 2012 Mar 26;52(3):844-56. doi: 10.1021/ci2004847. Epub 2012 Feb 23.

On the applicability of elastic network normal modes in small-molecule docking.

Author information

1
Max-Planck-Institut für Informatik, 66123 Saarbrücken, Germany. mdietzen@mpi-inf.mpg.de

Erratum in

  • J Chem Inf Model. 2014 Dec 22;54(12):3453.

Abstract

Incorporating backbone flexibility into protein-ligand docking is still a challenging problem. In protein-protein docking, normal mode analysis (NMA) has become increasingly popular as it can be used to describe the collective motions of a biological system, but the question of whether NMA can also be useful in predicting the conformational changes observed upon small-molecule binding has only been addressed in a few case studies. Here, we describe a large-scale study on the applicability of NMA for protein-ligand docking using 433 apo/holo pairs of the Astex data sets. On the basis of sets of the first normal modes from the apo structure, we first generated for each paired holo structure a set of conformations that optimally reproduce its C(α) trace with respect to the underlying normal mode subspace. Using AutoDock, GOLD, and FlexX we then docked the original ligands into these conformations to assess how the docking performance depends on the number of modes used to reproduce the holo structure. The results of our study indicate that, even for such a best-case scenario, the use of normal mode analysis in small-molecule docking is restricted and that a general rule on how many modes to use does not seem to exist or at least is not easy to find.

PMID:
22320151
DOI:
10.1021/ci2004847
[Indexed for MEDLINE]
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for American Chemical Society
    Loading ...
    Support Center