Title:Reliability of Virtual Screening Methods in Prediction of PDE4Binhibitor Activity
VOLUME: 12 ISSUE: 2
Author(s):Victoria Shubina, Sanna Niinivehmas and Olli T. Pentikainen
Affiliation:Department of Biological and Environmental Science, University of Jyvaskyla, P.O. Box 35, FI-40014 University of Jyvaskyla, Finland.
Keywords:Molecular docking, molecular mechanics-generalized born-surface area, pharmacophore
modeling, phosphodiesterase, three-dimensional quantitative structure-activity relationship, virtual
screening.
Abstract:Identification of active ligands using computational methods is a
challenging task. For example, molecular docking, pharmacophore modeling, and
three dimensional quantitative structure-activity relationship models (3D-QSAR) are widely used
methods to identify novel small molecules. However, all these methods have, in addition to
advantages, also significant pitfalls. The aim of this study was to compare some commonly used
computational methods to estimate their ability to separate highly active PDE4B-inhibitors from
less active and inactive ones. Here, 152 molecules with pIC50-range of 3.4-10.5, originating from
six original studies were used. High correlation coefficients by using docking, docking with postprocessing
with molecular mechanics-generalized Born-surface area -method (MMGBSA),
pharmacophore modeling, and 3D-QSAR were obtained. These results are well in line with earlier
studies done with similar methods, and suggest that computational methods could be successfully
used to identify novel PDE4B-inhibitors, especially if using multiple methods together.
