Bioenergetics: Open Access

Yi An

Publications

• Research Article
  Ensemble Molecular Dynamics of a Protein-Ligand Complex: Residual Inhibitor Entropy Enhances Drug Potency in Butyrylcholinesterase
  Author(s): Eric J Sorin, Walter Alvarado, Samantha Cao, Amethyst Radcliffe, Phuc La and Yi AnEric J Sorin, Walter Alvarado, Samantha Cao, Amethyst Radcliffe, Phuc La and Yi An
  
  Butyrylcholinesterase is a key enzyme that catalyzes the hydrolysis of the neurotransmitter acetylcholine and shows an increased activity in patients suffering from Alzheimer’s disease (AD), making this enzyme a primary target in treating AD. Central to this problem, and to similar scenarios involving biomolecular recognition, is our understanding of the nature of the protein-ligand complex. The butyrylcholinesterase enzyme was studied via all-atom, explicit solvent, ensemble molecular dynamics simulations sans inhibitor and in the presence of three dialkyl phenyl phosphate inhibitors of known potency to a cumulative sampling of over 40 μs. Following relaxation of these ensembles to conformational equilibria, binding modes for each inhibitor were identified. While classical models, which assume significant reduction in both protein and ligand conformational entropies, continu.. View More»
  DOI: 10.4172/2167-7662.1000145

  Abstract PDF