id	author	title	date	pages	extension	mime	words	sentences	flesch	summary	cache	txt
cord-282560-tofppr3b	Henderson, Jack A.	Assessment of proton-coupled conformational dynamics of SARS and MERS coronavirus papain-like proteases: Implication for designing broad-spectrum antiviral inhibitors	2020-09-21		.txt	text/plain	6242	332	56	Here, we report the pK(a) calculations and assessment of the proton-coupled conformational dynamics of SARS-CoV-2 in comparison to SARS-CoV and MERS-CoV PLpros using the recently developed graphical processing unit (GPU)-accelerated implicit-solvent continuous constant pH molecular dynamics method with a new asynchronous replica-exchange scheme, which allows computation on a single GPU card. 14, 15 Our previous work employing the hybrid-solvent based continuous constant pH molecular dynamics (CpHMD) simulations 16 demonstrated that the elucidation of proton-coupled conformational dynamics offers a deeper understanding of the structure-dynamics-function relationships 17 and inhibition mechanisms 18-20 of aspartyl proteases. We performed pH replica-exchange CpHMD simulations to estimate the pKa values of Asp/Glu/His/Cys/Lys side chains and assess possible proton-coupled dynamics in SARS-CoV, SARS-CoV-2, and MERS-CoV PLpros. To provide support for the protonation states determined by GB-CpHMD titrations and test the proton-coupled dynamics of the BL2 loop, we performed conventional all-atom fixed-charge MD simulations of SARS-CoV-2 PLpro with the catalytic side chains fixed in the charged states and Cys270 fixed in the protonated or deprotonated state.	./cache/cord-282560-tofppr3b.txt	./txt/cord-282560-tofppr3b.txt