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Updated: Mar 2, 2026

Analyzing Protein Architectures and Protein-Ligand Complexes by Integrative Structural Mass Spectrometry
Published on: October 15, 2018
Assessing protein-ligand binding modes with computational tools: the case of PDE4B
Gülşah Çifci1, Viktorya Aviyente1, E Demet Akten2
1Department of Chemistry, Boğaziçi University, 34342, Bebek, Istanbul, Turkey.
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].
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