High-throughput virtual screening and microsecond MD simulations to identify potential sugar mimic of the solute-binding protein BlAXBP of the ABC transporter from Bifidobacterium animalis subsp. Lactis |
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Affiliation: | 1. Department of Physics, University of Texas at San Antonio, San Antonio, TX 78249, USA;2. Department of Biology and Neurosciences Institute, University of Texas at San Antonio, San Antonio, TX 78249, USA;1. Department of Medicine, Division of Gastroenterology, Jewish General Hospital, McGill University School of Medicine, 3755 Cote Ste Catherine Road, Montreal, Quebec H3T 1E2, Canada;2. Department of Emergency Medicine, Jewish General Hospital, McGill University School of Medicine, 3755 Cote Ste Catherine Road, Montreal, Quebec H3T 1E2, Canada;1. School of Mathematics and Information Science, Anshan Normal University, Anshan, Liaoning, China;2. School of Computer Science and Technology, Dalian University of Technology, Dalian, Liaoning, China;3. School of Computer and Information Technology, Liaoning Normal University, Dalian, Liaoning, China;1. LIRMM – CNRS UMR 5506 Montpellier, France;2. Université de Sherbrooke, Canada |
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Abstract: | Xylotetraose is a prebiotic oligosaccharide can be utilized by the ABC transporter of the gut microbiota Bifidobacteria. BlAXBP is the solute binding protein of the ABC transporter, and its complex with xylotetraose has been solved by X-ray crystallography. Here, we have identified novel sugar mimic of BlAXBP by applying a high-throughput virtual screening of ZINC database containing a huge library with ∼22 M compounds. To begin with, we identified 18,571 ligands by a ligand-based virtual screening. Further, a total of 3968 compounds were selected for molecular docking due to their Tanimoto coefficient’s value were larger than a cutoff of 0.08. The molecular mechanics-generalized born surface area was used to evaluate the binding free energies, and the top 10 ligands with free energies below an energy threshold of -35.22 kcal/mol were selected. ZINC13783511 formed the most stable complex with BlAXBP and its recognition mechanism were further explored by microsecond MD simulations in explicit solvent. Free energy landscapes were used to evaluate conformational changes of BlAXBP in its ligand free and binding states. Collectively, this work identified potential novel sugar mimics to BlAXBP, providing novel atomic-level understanding of the binding mechanism. |
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Keywords: | Virtual screening Molecular docking MD simulations Prebiotics |
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