Implementing QM in docking calculations: is it a waste of computational time?
Related Experiment Video
Updated: Feb 27, 2026

Incorporating Target Protein Structure Flexibility and Dynamics in Computational Drug Discovery Using Ensemble-Based Docking Analysis
Published on: June 20, 2025
Adebayo A Adeniyi1, Mahmoud E S Soliman1
1School of Health Sciences, University of KwaZulu-Natal, Westville, Durban 4001, South Africa.
Abstract:
The greatest challenge in molecular docking (MD) is the deficiency of scoring functions (SFs), which limits their reliability. SFs are too simplified to represent the true features of the complex free energy of protein-ligand interactions. Investigations of docking functions have traded accuracy for speed through the use of approximations and simplifications. Consequently, there has been an increase in the popularity of quantum-mechanical (QM)-based methods as reference points for the development of fast, reliable, valuable, yet inexpensive, tools. As we discuss here, one significant QM-based parameter used to predict docking is the accuracy of atomic partial charges, which is strongly related to the accuracy of the SF prediction.
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