In light of these findings, we concluded that significant higher fusion rates were observed in patients who underwent posterior C1-C2 arthrodesis surgeries compared to those treated with anterior odontoid screw fixation.

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 the relaxation of these ensembles to conformational equilibria, binding modes for each inhibitor were identified. While classical models, which assume significant reduction in protein and ligand conformational entropies, continue to be favored in contemporary studies, our observations contradict those assumptions: bound ligands occupy many conformational states, thereby stabilizing the complex, while also promoting protein flexibility.

No abstract

Recent studies have shown that butyrylcholinesterase (BuChE) activity is increased in patients suffering from Alzheimer's disease (AD) and is one of the main enzyme targets necessary to treat Alzheimer's symptoms. As BuChE is a key enzyme that catalyzes the hydrolysis of the neurotransmitter acetylcholine, increased control over inhibition of this enzyme is highly sought. We employ molecular dynamics (MD) simulations to study the physics of the inhibitor‐enzyme complex and the chemical characteristics necessary to effectively target BuChE. One family of inhibitors is the dialkyl phenyl phosphates (DAPPs), which have been shown to specifically target BuChE. We studied the interactions and binding affinities of a number of DAPP's docked in the active site of BuChE. Using the Folding@Home Distributed Computing Network, 8,000 all‐atom molecular dynamics simulations were collected, including the enzyme sans inhibitor, which is used to evaluate the mechanism and energetics of ligand‐binding, as well as the equilibrium dynamics of the enzyme‐substrate complex.This work was made possible by the worldwide Folding@Home volunteers who contributed invaluable processor time; Women & Philanthropy, Kenneth L. Marsi, and James L. Jensen Student Scholarships; and a Research Corporation Cottrell College Science Award.