Application of InterCriteria Analysis to Assess the Performance of Scoring Functions in Molecular Docking Software Packages

Dessislava Jereva, Petko Alov, Ivanka Tsakovska, Maria Angelova, Vassia Atanassova, Peter Vassilev, Nikolay Ikonomov, Krassimir Atanassov, Ilza Pajeva and Tania Pencheva
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Dessislava Jereva: Department of QSAR and Molecular Modelling, Institute of Biophysics and Biomedical Engineering, Bulgarian Academy of Sciences, 1113 Sofia, Bulgaria
Petko Alov: Department of QSAR and Molecular Modelling, Institute of Biophysics and Biomedical Engineering, Bulgarian Academy of Sciences, 1113 Sofia, Bulgaria
Ivanka Tsakovska: Department of QSAR and Molecular Modelling, Institute of Biophysics and Biomedical Engineering, Bulgarian Academy of Sciences, 1113 Sofia, Bulgaria
Maria Angelova: Department of QSAR and Molecular Modelling, Institute of Biophysics and Biomedical Engineering, Bulgarian Academy of Sciences, 1113 Sofia, Bulgaria
Vassia Atanassova: Department of Bioinformatics and Mathematical Modelling, Institute of Biophysics and Biomedical Engineering, Bulgarian Academy of Sciences, 1113 Sofia, Bulgaria
Peter Vassilev: Department of Bioinformatics and Mathematical Modelling, Institute of Biophysics and Biomedical Engineering, Bulgarian Academy of Sciences, 1113 Sofia, Bulgaria
Nikolay Ikonomov: Department of Software Engineering and Information Systems, Institute of Mathematics and Informatics, Bulgarian Academy of Sciences, 1113 Sofia, Bulgaria
Krassimir Atanassov: Department of Bioinformatics and Mathematical Modelling, Institute of Biophysics and Biomedical Engineering, Bulgarian Academy of Sciences, 1113 Sofia, Bulgaria
Ilza Pajeva: Department of QSAR and Molecular Modelling, Institute of Biophysics and Biomedical Engineering, Bulgarian Academy of Sciences, 1113 Sofia, Bulgaria
Tania Pencheva: Department of QSAR and Molecular Modelling, Institute of Biophysics and Biomedical Engineering, Bulgarian Academy of Sciences, 1113 Sofia, Bulgaria

Mathematics, 2022, vol. 10, issue 15, 1-17

Abstract: (1) Background: In silico approaches to rational drug design are among the fastest evolving ones. Depending on the available structural information for the biomacromolecule and the small molecule, the in silico methods are classified as ligand- and structure-based. The latter predict ligand–receptor binding using 3D structures of both molecules, whose computational simulation is referred to as molecular docking. It aims at estimating the binding affinity (approximated by scoring function) and the ligand binding pose in the receptor’s active site, which postulates a key role of the scoring functions in molecular docking algorithms. This study focuses on the performance of different types of scoring functions implemented in molecular modelling software packages. (2) Methods: An InterCriteria analysis (ICrA) was applied to assess the performance of the scoring functions available in MOE, GOLD, SeeSAR, and AutoDock Vina software platforms. The InterCriteria analysis was developed to distinguish possible relations between pairs of criteria when multiple objects are considered. All 12 investigated scoring functions were tested by docking a set of protease inhibitors in the binding sites of two protein targets. The dataset consisted of 88 benzamidine-type compounds with experimentally measured inhibitory constants for thrombin and trypsin, which allows for the objective assessment of the scoring functions performance. The results generated by the molecular docking were subjected to ICrA in order to analyze both docking energies as approximations of the binding affinities and RMSDs (root-mean-square deviation) as measures of the experimental binding pose proximity between the compounds and the co-crystalized ligand, based on the atoms in the common scaffold. (3) Results: The results obtained for the best poses, the average of the best 5 or 30 poses retained after docking, were analyzed. A comparison with the experimentally observed inhibitory effects was also performed. The InterCriteria analysis application confirms that the performance of the scoring functions for the same dataset of ligands depends on the studied protein. The analysis reveals that none of the studied scoring functions is a good predictor of the compounds’ binding affinities for the considered protein targets. (4) Conclusion: In terms of this analysis, the investigated scoring functions do not produce equivalent results, which suggests the necessity for their combined use in consensus docking studies.

Keywords: InterCriteria analysis; molecular docking; scoring function; decision making (search for similar items in EconPapers)
JEL-codes: C (search for similar items in EconPapers)
Date: 2022
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