Electrostatic Contributions to the Binding Free Energy of Nicotine to the Acetylcholine Binding Protein.

ABSTRACT: Biomolecular binding relies on specific attractive interactions between two partner molecules, including electrostatics, dispersion, hydrophobicity, and solvation. Assessing the contributions of electrostatic interactions to binding is key to the understanding of ligand binding mechanisms and the design of improved biomolecular binders. For example, nicotine is a well-known agonist of nicotinic acetylcholine receptors (nAChRs), but the molecular mechanisms for the differential action of nicotine on brain and muscle nAChRs remain elusive. In this work, we have chosen the acetylcholine binding protein (AChBP) in complex with nicotine as a model system to interrogate the electrostatic contributions to nicotine binding. Our absolute binding free energy simulations confirm that nicotine binds A

SUBMITTER: Li Z 

PROVIDER: S-EPMC10056799 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature