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Int. J. Mol. Sci. 2016, 17(4), 525; doi:10.3390/ijms17040525

Is It Reliable to Use Common Molecular Docking Methods for Comparing the Binding Affinities of Enantiomer Pairs for Their Protein Target?

Centro de Bioinformática y Simulación Molecular (CBSM), Universidad de Talca. 2 Norte 685, Casilla 721, Talca, Chile
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Academic Editors: Humberto González-Díaz, Roberto Todeschini and Alejandro Pazos Sierra
Received: 22 February 2016 / Revised: 22 March 2016 / Accepted: 1 April 2016 / Published: 20 April 2016
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Abstract

Molecular docking is a computational chemistry method which has become essential for the rational drug design process. In this context, it has had great impact as a successful tool for the study of ligand–receptor interaction modes, and for the exploration of large chemical datasets through virtual screening experiments. Despite their unquestionable merits, docking methods are not reliable for predicting binding energies due to the simple scoring functions they use. However, comparisons between two or three complexes using the predicted binding energies as a criterion are commonly found in the literature. In the present work we tested how wise is it to trust the docking energies when two complexes between a target protein and enantiomer pairs are compared. For this purpose, a ligand library composed by 141 enantiomeric pairs was used, including compounds with biological activities reported against seven protein targets. Docking results using the software Glide (considering extra precision (XP), standard precision (SP), and high-throughput virtual screening (HTVS) modes) and AutoDock Vina were compared with the reported biological activities using a classification scheme. Our test failed for all modes and targets, demonstrating that an accurate prediction when binding energies of enantiomers are compared using docking may be due to chance. We also compared pairs of compounds with different molecular weights and found the same results. View Full-Text
Keywords: molecular docking; modeling of enantiomers; prediction capability; docking accuracy; docking scoring; binding affinities molecular docking; modeling of enantiomers; prediction capability; docking accuracy; docking scoring; binding affinities
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Ramírez, D.; Caballero, J. Is It Reliable to Use Common Molecular Docking Methods for Comparing the Binding Affinities of Enantiomer Pairs for Their Protein Target? Int. J. Mol. Sci. 2016, 17, 525.

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