Mapping Free Energy Pathways for ATP Hydrolysis in the E. coli ABC Transporter HlyB by the String Method

dc.contributor.authorZhou, Yan
dc.contributor.authorOjeda-May, Pedro
dc.contributor.authorNagaraju, Mulpuri
dc.contributor.authorKim, Bryant
dc.contributor.authorPu, Jingzhi
dc.contributor.departmentChemistry and Chemical Biology, School of Scienceen_US
dc.date.accessioned2019-06-28T17:24:13Z
dc.date.available2019-06-28T17:24:13Z
dc.date.issued2018-10-16
dc.description.abstractHlyB functions as an adenosine triphosphate (ATP)-binding cassette (ABC) transporter that enables bacteria to secrete toxins at the expense of ATP hydrolysis. Our previous work, based on potential energy profiles from combined quantum mechanical and molecular mechanical (QM/MM) calculations, has suggested that the highly conserved H-loop His residue H662 in the nucleotide binding domain (NBD) of E. coli HlyB may catalyze the hydrolysis of ATP through proton relay. To further test this hypothesis when entropic contributions are taken into account, we obtained QM/MM minimum free energy paths (MFEPs) for the HlyB reaction, making use of the string method in collective variables. The free energy profiles along the MFEPs confirm the direct participation of H662 in catalysis. The MFEP simulations of HlyB also reveal an intimate coupling between the chemical steps and a local protein conformational change involving the signature-loop residue S607, which may serve a catalytic role similar to an Arg-finger motif in many ATPases and GTPases in stabilizing the phosphoryl-transfer transition state.en_US
dc.eprint.versionFinal published versionen_US
dc.identifier.citationZhou, Y., Ojeda-May, P., Nagaraju, M., Kim, B., & Pu, J. (2018). Mapping Free Energy Pathways for ATP Hydrolysis in the E. coli ABC Transporter HlyB by the String Method. Molecules (Basel, Switzerland), 23(10), 2652. doi:10.3390/molecules23102652en_US
dc.identifier.urihttps://hdl.handle.net/1805/19754
dc.language.isoen_USen_US
dc.publisherMDPIen_US
dc.relation.isversionof10.3390/molecules23102652en_US
dc.relation.journalMolecules (Basel, Switzerland)en_US
dc.rightsAttribution 3.0 United States*
dc.rights.urihttp://creativecommons.org/licenses/by/3.0/us/*
dc.sourcePMCen_US
dc.subjectABC transporteren_US
dc.subjectATP hydrolysisen_US
dc.subjectQM/MMen_US
dc.subjectFree energy simulationsen_US
dc.subjectMinimum free energy pathen_US
dc.subjectProton transferen_US
dc.subjectString methoden_US
dc.titleMapping Free Energy Pathways for ATP Hydrolysis in the E. coli ABC Transporter HlyB by the String Methoden_US
dc.typeArticleen_US
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