4D-QSAR and MIA-QSAR study on the Bruton's tyrosine kinase (Btk) inhibitors

J Mol Graph Model. 2019 Nov:92:357-362. doi: 10.1016/j.jmgm.2019.08.009. Epub 2019 Aug 18.

Abstract

In this paper, 4D-QSAR analysis base on LQTA-QSAR method and MIA-QSAR analysis were presented. And a combination model of 4D-QSAR model and MIA-QSAR model with better predictive performance was built. The 4D-QSAR descriptors were obtained by calculating the interaction energies between the probes and aligned conformational ensemble profiles (CEP) resulting from molecular dynamics simulation. The MIA descriptors were generated from aligned images of chemical structure. Those descriptors were filtered and employed in partial least squares (PLS) regression. The combination model was built by the merging the descriptors generated by the two methods of 4D-QSAR and MIA-QSAR analysis. Those models were built using programs written by authors, and anyone can download those programs at https://github.com/masgils.

Keywords: 4D-QSAR; Btk inhibitors; Combination model; Design and model programs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Agammaglobulinaemia Tyrosine Kinase / antagonists & inhibitors
  • Agammaglobulinaemia Tyrosine Kinase / chemistry*
  • Algorithms
  • Drug Discovery
  • Molecular Conformation
  • Molecular Docking Simulation*
  • Molecular Dynamics Simulation*
  • Protein Kinase Inhibitors / chemistry*
  • Protein Kinase Inhibitors / pharmacology
  • Quantitative Structure-Activity Relationship*

Substances

  • Protein Kinase Inhibitors
  • Agammaglobulinaemia Tyrosine Kinase