id	author	title	date	pages	extension	mime	words	sentences	flesch	summary	cache	txt
cord-103876-2rg2qtdq	Watkins, Laura C.	Influenza A M2 Inhibitor Binding Understood through Mechanisms of Excess Proton Stabilization and Channel Dynamics	2020-06-20		.txt	text/plain	5528	249	47	In this work, we test the hypothesis that these drugs act primarily as mechanism-based inhibitors by comparing hydrated excess proton stabilization during proton transport in M2 with the interactions revealed in the crystal structures, using the Multiscale Reactive Molecular Dynamics (MS-RMD) methodology. Along with an earlier qualitative MD simulation study that guided the design of the spiro-adamantyl amine inhibitors, 41 the crystallographic analysis provided potential insights into the mechanism of inhibition, suggesting that the backbone carbonyls of pore-lining residues act as physiochemical chameleons, able to engage in both hydrophobic and hydrophilic interactions, and that the drug is tilted off the channel's axis and interacts with waters in the Ala30 layer. Most recently, we further analyzed the MS-RMD simulations to explore the detailed interactions between the hydrated excess proton and the channel and found that the proton dynamically, as a function of its position, alters several properties of the protein and pore waters, including the hydrogen-bonding network and the protein structure.	./cache/cord-103876-2rg2qtdq.txt	./txt/cord-103876-2rg2qtdq.txt