title: In Silico Analysis of Binding Interaction of Mamba Toxins with M4 and M2 Muscarinic Acetylcholine Receptors for Therapeutic Use in Alzheimer's Disease.
abstract: Muscarinic acetylcholine receptors are stimulated by the neurotransmitter acetylcholine and are involved in various functions across the human body. These receptors have surfaced for their potential use as targets in treatment of Alzheimer's disease. Muscarinic receptors have been reported to show binding interaction with various mamba toxins, such as dendrotoxins and muscarinic toxins that act as antagonists of these receptors. Therefore, in our study we have focused on the binding analysis of these mamba toxins with the M4 and M2 muscarinic acetylcholine autoreceptors for their potential use as targets in treating cognitive symptoms associated with Alzheimer's disease. A ligand dataset was developed that consisted of dendrotoxins and muscarinic toxins originating from various mamba species. Receptor dataset consisted of M4 and M2 muscarinic acetylcholine autoreceptors. Docking studies were performed using AutoDock 4.2 between these ligands with each receptor and further analysis was done using various computational tools. Docking experiments were performed and analyzed to check the binding compatibilities between mamba toxins and muscarinic acetylcholine autoreceptors. Detail analysis revealed that these ligands bind to active site residues of both receptors. Therefore by these in silico results, we suggest that the mamba toxins can be potential antagonists of the M4 and M2 muscarinic acetylcholine autoreceptors.
authors: Maleeha
authors: M
authors: Waqar
authors: Mohammad Amjad
authors: MA
authors: Kamal
authors: Department of BioSciences, COMSATS Institute of Information Technology, Park Road, Chak Shahzad Islamabad-44000, Pakistan. sidra.batool@comsats.edu.pk.
authors: Sidra
authors: S
authors: Batool
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy*; D000595:Amino Acid Sequence; D001665:Binding Sites; D004546:Elapid Venoms / Q000494:pharmacology*; D006801:Humans; D006860:Hydrogen Bonding; D057927:Hydrophobic and Hydrophilic Interactions; D062105:Molecular Docking Simulation; D008969:Molecular Sequence Data; D018727:Muscarinic Antagonists / Q000494:pharmacology*; D043585:Receptor, Muscarinic M2 / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000235:genetics; D043588:Receptor, Muscarinic M4 / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000235:genetics; D016415:Sequence Alignment
chemical_list: D004546:Elapid Venoms; D018727:Muscarinic Antagonists; D043585:Receptor, Muscarinic M2; D043588:Receptor, Muscarinic M4