Matches in SemOpenAlex for { <https://semopenalex.org/work/W2620831429> ?p ?o ?g. }
- W2620831429 endingPage "6312" @default.
- W2620831429 startingPage "6295" @default.
- W2620831429 abstract "In the context of the SIBFA polarizable molecular mechanics/dynamics (PMM/PMD) procedure, we report the calibration and a series of validation tests for the 1,2,4-triazole-3-thione (TZT) heterocycle. TZT acts as the chelating group of inhibitors of dizinc metallo-β-lactamases (MBL), an emerging class of Zn-dependent bacterial enzymes, which by cleaving the β-lactam bond of most β-lactam antibiotics are responsible for the acquired resistance of bacteria to these drugs. Such a study is indispensable prior to performing PMD simulations of complexes of TZT-based inhibitors with MBL’s, on account of the anchoring role of TZT in the dizinc MBL recognition site. Calibration was done by comparisons to energy decomposition analyses (EDA) of high-level ab initio QC computations of the TZT complexes with two probes: Zn(II), representative of “soft” dications, and water, representative of dipolar molecules. We performed distance variations of the approach of each probe to each of the two TZT atoms involved in Zn ligation, the S atom and the N atom ortho to it, so that each SIBFA contribution matches its QC counterpart. Validations were obtained by performing in- and out-of-plane angular variations of Zn(II) binding in monoligated Zn(II)–TZT complexes. The most demanding part of this study was then addressed. How well does ΔE(SIBFA) and its individual contributions compare to their QC counterparts in the dizinc binding site of one MBL, L1, whose structure is known from high-resolution X-ray crystallography? Six distinct complexes were considered, namely each separate monozinc site, and the dizinc site, whether ligated or unligated by TZT. Despite the large magnitude of the interaction energies, in all six complexes ΔE(SIBFA) can match ΔE(QC) with relative errors <2% and the proper balance of individual energy contributions. The computations were extended to the dizinc site of another MBL, VIM-2, and its complexes with two other TZT analogues. ΔE(SIBFA) faithfully reproduced ΔE(QC) in terms of magnitude, ranking of the three ligands, and trends of the separate energy contributions. A preliminary extension to correlated calculations is finally presented. All these validations should enable a secure design of a diversity of TZT-containing MBL inhibitors: a structurally and energetically correct anchoring of TZT should enable all other inhibitor groups to in turn optimize their interactions with the other target MBL residues." @default.
- W2620831429 created "2017-06-09" @default.
- W2620831429 creator A5001358189 @default.
- W2620831429 creator A5012672067 @default.
- W2620831429 creator A5013022449 @default.
- W2620831429 creator A5015298513 @default.
- W2620831429 creator A5036142396 @default.
- W2620831429 creator A5041485767 @default.
- W2620831429 creator A5055429261 @default.
- W2620831429 creator A5058834773 @default.
- W2620831429 creator A5073132719 @default.
- W2620831429 creator A5079049821 @default.
- W2620831429 creator A5079966436 @default.
- W2620831429 date "2017-06-22" @default.
- W2620831429 modified "2023-10-05" @default.
- W2620831429 title "Calibration of 1,2,4-Triazole-3-Thione, an Original Zn-Binding Group of Metallo-β-Lactamase Inhibitors. Validation of a Polarizable MM/MD Potential by Quantum Chemistry" @default.
- W2620831429 cites W1594633721 @default.
- W2620831429 cites W1963483960 @default.
- W2620831429 cites W1969432389 @default.
- W2620831429 cites W1969616449 @default.
- W2620831429 cites W1988920524 @default.
- W2620831429 cites W1989474096 @default.
- W2620831429 cites W1994144563 @default.
- W2620831429 cites W1995176305 @default.
- W2620831429 cites W1996846370 @default.
- W2620831429 cites W1999864020 @default.
- W2620831429 cites W2004488094 @default.
- W2620831429 cites W2004899073 @default.
- W2620831429 cites W2005600183 @default.
- W2620831429 cites W2009616314 @default.
- W2620831429 cites W2019438068 @default.
- W2620831429 cites W2022950330 @default.
- W2620831429 cites W2026172453 @default.
- W2620831429 cites W2034998953 @default.
- W2620831429 cites W2035472798 @default.
- W2620831429 cites W2038583777 @default.
- W2620831429 cites W2039741320 @default.
- W2620831429 cites W2039746939 @default.
- W2620831429 cites W2039786868 @default.
- W2620831429 cites W2046855998 @default.
- W2620831429 cites W2049819418 @default.
- W2620831429 cites W2050206511 @default.
- W2620831429 cites W2056026687 @default.
- W2620831429 cites W2058678123 @default.
- W2620831429 cites W2058775963 @default.
- W2620831429 cites W2059346121 @default.
- W2620831429 cites W2065337857 @default.
- W2620831429 cites W2069006374 @default.
- W2620831429 cites W2069218335 @default.
- W2620831429 cites W2071157096 @default.
- W2620831429 cites W2085526888 @default.
- W2620831429 cites W2092157292 @default.
- W2620831429 cites W2093914988 @default.
- W2620831429 cites W2103332767 @default.
- W2620831429 cites W2104650602 @default.
- W2620831429 cites W2111719244 @default.
- W2620831429 cites W2113518689 @default.
- W2620831429 cites W2123735033 @default.
- W2620831429 cites W2139363454 @default.
- W2620831429 cites W2148941593 @default.
- W2620831429 cites W2149105617 @default.
- W2620831429 cites W2159038065 @default.
- W2620831429 cites W2164502401 @default.
- W2620831429 cites W2165321807 @default.
- W2620831429 cites W2294872877 @default.
- W2620831429 cites W2312714072 @default.
- W2620831429 cites W2323098947 @default.
- W2620831429 cites W2332379983 @default.
- W2620831429 cites W2335172671 @default.
- W2620831429 cites W2335207279 @default.
- W2620831429 cites W2406265752 @default.
- W2620831429 cites W2529135769 @default.
- W2620831429 cites W2598078437 @default.
- W2620831429 cites W2618864169 @default.
- W2620831429 cites W2963647810 @default.
- W2620831429 cites W4230014612 @default.
- W2620831429 cites W4235995681 @default.
- W2620831429 cites W4244626184 @default.
- W2620831429 doi "https://doi.org/10.1021/acs.jpcb.7b01053" @default.
- W2620831429 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/28574718" @default.
- W2620831429 hasPublicationYear "2017" @default.
- W2620831429 type Work @default.
- W2620831429 sameAs 2620831429 @default.
- W2620831429 citedByCount "11" @default.
- W2620831429 countsByYear W26208314292019 @default.
- W2620831429 countsByYear W26208314292020 @default.
- W2620831429 countsByYear W26208314292021 @default.
- W2620831429 countsByYear W26208314292022 @default.
- W2620831429 crossrefType "journal-article" @default.
- W2620831429 hasAuthorship W2620831429A5001358189 @default.
- W2620831429 hasAuthorship W2620831429A5012672067 @default.
- W2620831429 hasAuthorship W2620831429A5013022449 @default.
- W2620831429 hasAuthorship W2620831429A5015298513 @default.
- W2620831429 hasAuthorship W2620831429A5036142396 @default.
- W2620831429 hasAuthorship W2620831429A5041485767 @default.
- W2620831429 hasAuthorship W2620831429A5055429261 @default.
- W2620831429 hasAuthorship W2620831429A5058834773 @default.
- W2620831429 hasAuthorship W2620831429A5073132719 @default.