Binding Space Concept: A New Approach To Enhance the Reliability of Docking Scores and Its Application to Predicting Butyrylcholinesterase Hydrolytic Activity
| العنوان: | Binding Space Concept: A New Approach To Enhance the Reliability of Docking Scores and Its Application to Predicting Butyrylcholinesterase Hydrolytic Activity |
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| المؤلفون: | Giulio Vistoli, Bernard Testa, Angelica Mazzolari, Alessandro Pedretti |
| المصدر: | Journal of Chemical Information and Modeling. 57:1691-1702 |
| بيانات النشر: | American Chemical Society (ACS), 2017. |
| سنة النشر: | 2017 |
| مصطلحات موضوعية: | 0301 basic medicine, Protein Conformation, Computer science, General Chemical Engineering, Binding pocket, Library and Information Sciences, Ligands, 01 natural sciences, 03 medical and health sciences, Humans, Lead Finder, Ligand, business.industry, Hydrolysis, General Chemistry, 0104 chemical sciences, Computer Science Applications, Molecular Docking Simulation, 010404 medicinal & biomolecular chemistry, 030104 developmental biology, Protein–ligand docking, Docking (molecular), Searching the conformational space for docking, Butyrylcholinesterase, Artificial intelligence, Biological system, business, Protein Binding |
| الوصف: | Docking simulations are very popular approaches able to assess the capacity of a given ligand to interact with a target. Docking simulations are usually focused on a single best complex even though many studies showed that ligands retain a significant mobility within a binding pocket by assuming different binding modes all of which may contribute to the monitored ligand affinity. The present study describes an innovative concept, the binding space, which allows an exploration of the ligand mobility within the binding pocket by simultaneously considering several ligand poses as generated by docking simulations. The multiple poses and the relative docking scores can then be analyzed by taking advantage of the same concepts already used in the property space analysis; hence the binding space can be parametrized by (a) mean scores, (b) score ranges, and (c) score sensitivity values. The first parameter represents a very simple procedure to account for the contribution of the often neglected alternative binding modes, while the last two descriptors encode the degree of mobility which a given ligand retains within the binding cavity (score range) as well as the ease with which a ligand explores such a mobility (score sensitivity). Here, the binding space concept is applied to the prediction of the hydrolytic activity of BChE by synergistically considering multiple poses and multiple protein structures. The obtained results shed light on the remarkable potential of the binding space concept, whose parameters allow a significant increase of the predictive power of the docking results as revealed by extended correlative analyses. Mean scores are the parameters affording the largest statistical improvement, and all the here proposed docking-based descriptors show enhancing effects in developing predictive models. Finally, the study describes a new score function (Contacts score) simply based on the number of surrounding residues which appears to be particularly productive in the framework of the binding space. |
| تدمد: | 1549-960X 1549-9596 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::3eda463625f625681352262a12f92241 https://doi.org/10.1021/acs.jcim.7b00121 |
| رقم الأكسشن: | edsair.doi.dedup.....3eda463625f625681352262a12f92241 |
| قاعدة البيانات: | OpenAIRE |
Find this issue from the American Chemical Society | تدمد: | 1549960X 15499596 |
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