Docking and scoring with ICM: the benchmarking results and strategies for improvement

By Marco A. C. Neves, Maxim Totrov, Ruben Abagyan. Journal of Computer-Aided Molecular Design, 2012

350 citations recorded by the source corpus.

Flexible docking and scoring using the internal coordinate mechanics software (ICM) was benchmarked for ligand binding mode prediction against the 85 co-crystal structures in the modified Astex data set. The ICM virtual ligand screening was tested against the 40 DUD target benchmarks and 11-target WOMBAT sets. The self-docking accuracy was evaluated for the top 1 and top 3 scoring poses at each ligand binding site with near native conformations below 2 Å RMSD found in 91 and 95% of the predictions, respectively. The virtual ligand screening using single rigid pocket conformations provided the median area under the ROC curves equal to 69.4 with 22.0% true positives recovered at 2% false positive rate. Significant improvements up to ROC AUC = 82.2 and ROC(2%) = 45.2 were achieved following our best practices for flexible pocket refinement and out-of-pocket binding rescore. The virtual screening can be further improved by considering multiple conformations of the target.

Subfields: Computational Theory and Mathematics, Materials Chemistry, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/84f03eff15aa39c99e6cecdd991f48585b30fb4a

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Citations in the corpus

Fast Docking on Graphics Processing Units via Ray-Casting (2013, background): “Most approaches fix the receptor conformation or allow only limited conformational changes during docking, to reduce the number of degrees of freedom associated with the search [7–11].”
Protein-ligand docking in the new millennium--a retrospective of 10 years in the field. (2013, background): “Neves & co-workers [209] have analyzed also the performance of ICM against the 85 co-crystal structures of ASTEX.”
Structure-Based Virtual Screening for Drug Discovery: Principles, Applications and Recent Advances (2014, methodology): “have investigated the ICM flexible docking and scoring benchmarks for 85 co-crystal structures of the modified Astex data set and derived significant improvements, compared to single rigid docking [94].”
Analysis of therapeutic targets for SARS-CoV-2 and discovery of potential drugs by computational methods (2020, neutral): “The score of ICM software is calculated by the overall empirical function of predicted physical interaction, whiles the mfScore (mean force Score) is computed by the knowledge-based potential functions derived from statistics of ligand e receptor complex in PDB 50,51 .”
Computational approaches streamlining drug discovery (2023, methodology): “The docking procedure itself can use molecular mechanics, often in internal coordinate representation, for rapid conformational sampling of fully flexible ligands 52,53 , using empirical 3D shape-matching approaches 54,55 , or combining them in a hybrid docking funnel 56,57 .”
Ligand Pose and Orientational Sampling in Molecular Docking (2013, methodology): “ICM [70] uses multiple stochastic runs to sample poses to be scored with an energy function, while GOLD [71] uses a genetic algorithm to sample poses and includes a variety of scoring functions.”
Ligand-biased ensemble receptor docking (LigBEnD): a hybrid ligand/receptor structure-based approach (2017, methodology): “They were re-evaluated using ICM’s standard VLS docking score SDock which is a GBSA/MM-type scoring function augmented with a directional hydrogen bonding term [17].”