{Reference Type}: Journal Article
{Title}: Assessing protein-ligand binding modes with computational tools: the case of PDE4B.
{Author}: Çifci G;Aviyente V;Akten ED;Monard G;
{Journal}: J Comput Aided Mol Des
{Volume}: 31
{Issue}: 6
{Year}: Jun 2017
{Factor}: 4.179
{DOI}: 10.1007/s10822-017-0024-7
{Abstract}: In a first step in the discovery of novel potent inhibitor structures for the PDE4B family with limited side effects, we present a protocol to rank newly designed molecules through the estimation of their IC[Formula: see text] values. Our protocol is based on reproducing the linear relationship between the logarithm of experimental IC[Formula: see text] values [[Formula: see text](IC[Formula: see text])] and their calculated binding free energies ([Formula: see text]). From 13 known PDE4B inhibitors, we show here that (1) binding free energies obtained after a docking process by AutoDock are not accurate enough to reproduce this linear relationship; (2) MM-GB/SA post-processing of molecular dynamics (MD) trajectories of the top ranked AutoDock pose improves the linear relationship; (3) by taking into account all representative structures obtained by AutoDock and by averaging MM-GB/SA computations on a series of 40 independent MD trajectories, a linear relationship between [Formula: see text](IC[Formula: see text]) and the lowest [Formula: see text] is achieved with [Formula: see text].