QSAR Models Guided by Molecular Dynamics Applied to Human Glucokinase Activators

Chem Biol Drug Des. 2016 Mar;87(3):455-66. doi: 10.1111/cbdd.12683. Epub 2015 Dec 16.

Abstract

In this study, quantitative structure-activity relationship studies which make use of molecular dynamics trajectories were performed on a set of 54 glucokinase protein activators. The conformations obtained by molecular dynamics simulation were superimposed according to the twelve alignments tested in a virtual three-dimensional box comprised of 2 Å cells. The models were generated by the technique that combines genetic algorithms and partial least squares. The best alignment models generated with a determination coefficient (r(2)) between 0.674 and 0.743 and cross-validation (q(2)) between 0.509 and 0.610, indicating good predictive capacity. The 4D-QSAR models developed in this study suggest novel molecular regions to be explored in the search for better glucokinase activators.

Keywords: diabetes mellitus; glucokinase; glucokinase activators and 4D-QSAR; type 2 diabetes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Enzyme Activation
  • Glucokinase / metabolism*
  • Humans
  • Molecular Dynamics Simulation
  • Quantitative Structure-Activity Relationship

Substances

  • Glucokinase