title: Molecular simulation of N-acetylneuraminic acid analogs and molecular dynamics studies of cholera toxin-Neu5Gc complex.
abstract: Cholera toxin (CT) is an AB5 protein complex secreted by the pathogen Vibrio cholera, which is responsible for cholera infection. N-acetylneuraminic acid (NeuNAc) is a derivative of neuraminic acid with nine-carbon backbone. NeuNAc is distributed on the cell surface mainly located in the terminal components of glycoconjugates, and also plays an important role in cell-cell interaction. In our current study, molecular docking and molecular dynamic (MD) simulations were implemented to identify the potent NeuNAc analogs with high-inhibitory activity against CT protein. Thirty-four NeuNAc analogs, modified in different positions C-1/C-2/C-4/C-5/C-7/C-8/C-9, were modeled and docked against the active site of CT protein. Among the 34 NeuNAc analogs, the analog Neu5Gc shows the least extra precision glide score of -9.52 and glide energy of -44.71 kcal/mol. NeuNAc analogs block the CT active site residues HIS:13, ASN:90, LYS:91, GLN:56, GLN:61, and TRP:88 through intermolecular hydrogen bonding. The MD simulation for CT-Neu5Gc docking complex was performed using Desmond. MD simulation of CT-Neu5Gc complex reveals the stable nature of docking interaction.
authors.affiliation: a Department of Bioinformatics , Karunya Univesity , Karunya Nagar, Coimbatore 641114 , Tamil Nadu , India.
authors.forename: J Jino
authors.initials: JJ
authors.lastname: Blessy
authors.forename: D Jeya Sundara
authors.initials: DJ
authors.lastname: Sharmila
mesh_terms: D001665:Binding Sites; D002772:Cholera Toxin / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000378:metabolism; D008968:Molecular Conformation; D062105:Molecular Docking Simulation; D056004:Molecular Dynamics Simulation; D015394:Molecular Structure; D019158:N-Acetylneuraminic Acid / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D011485:Protein Binding; D012794:Sialic Acids / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology
chemical_list: C078888:N-(O-acetyl)glycoloylneuraminic acid; D012794:Sialic Acids; D002772:Cholera Toxin; D019158:N-Acetylneuraminic Acid
keywords: NeuNAc analogs; cholera toxin; docking; molecular dynamics