Your browser doesn't support javascript.
Interfacial Water Many-Body Effects Drive Structural Dynamics and Allosteric Interactions in SARS-CoV-2 Main Protease Dimerization Interface.
El Ahdab, Dina; Lagardère, Louis; Inizan, Théo Jaffrelot; Célerse, Fréderic; Liu, Chengwen; Adjoua, Olivier; Jolly, Luc-Henri; Gresh, Nohad; Hobaika, Zeina; Ren, Pengyu; Maroun, Richard G; Piquemal, Jean-Philip.
  • El Ahdab D; Sorbonne Université, LCT, UMR 7616 CNRS, 75005 Paris, France.
  • Lagardère L; Université Saint-Joseph de Beyrouth, UR EGP, Centre d'Analyses et de Recherche, Faculté des Sciences, 1104 2020 Beirut, Lebanon.
  • Inizan TJ; Sorbonne Université, LCT, UMR 7616 CNRS, 75005 Paris, France.
  • Célerse F; Sorbonne Université, IP2CT, FR 2622 CNRS, 75005 Paris, France.
  • Liu C; Sorbonne Université, LCT, UMR 7616 CNRS, 75005 Paris, France.
  • Adjoua O; Sorbonne Université, LCT, UMR 7616 CNRS, 75005 Paris, France.
  • Jolly LH; Sorbonne Université, IPCM, UMR 8232 CNRS, 75005 Paris, France.
  • Gresh N; Department of Biomedical Engineering, University of Texas at Austin, Austin, Texas 78712, United States.
  • Hobaika Z; Sorbonne Université, LCT, UMR 7616 CNRS, 75005 Paris, France.
  • Ren P; Sorbonne Université, IP2CT, FR 2622 CNRS, 75005 Paris, France.
  • Maroun RG; Sorbonne Université, LCT, UMR 7616 CNRS, 75005 Paris, France.
  • Piquemal JP; Université Saint-Joseph de Beyrouth, UR EGP, Centre d'Analyses et de Recherche, Faculté des Sciences, 1104 2020 Beirut, Lebanon.
J Phys Chem Lett ; 12(26): 6218-6226, 2021 Jul 08.
Article in English | MEDLINE | ID: covidwho-1387122
ABSTRACT
Following our previous work ( Chem. Sci. 2021, 12, 4889-4907), we study the structural dynamics of the SARS-CoV-2 Main Protease dimerization interface (apo dimer) by means of microsecond adaptive sampling molecular dynamics simulations (50 µs) using the AMOEBA polarizable force field (PFF). This interface is structured by a complex H-bond network that is stable only at physiological pH. Structural correlations analysis between its residues and the catalytic site confirms the presence of a buried allosteric site. However, noticeable differences in allosteric connectivity are observed between PFFs and non-PFFs. Interfacial polarizable water molecules are shown to appear at the heart of this discrepancy because they are connected to the global interface H-bond network and able to adapt their dipole moment (and dynamics) to their diverse local physicochemical microenvironments. The water-interface many-body interactions appear to drive the interface volume fluctuations and to therefore mediate the allosteric interactions with the catalytic cavity.
Subject(s)

Full text: Available Collection: International databases Database: MEDLINE Main subject: Water / Viral Matrix Proteins / Molecular Dynamics Simulation / SARS-CoV-2 Type of study: Experimental Studies Limits: Humans Language: English Journal: J Phys Chem Lett Year: 2021 Document Type: Article Affiliation country: ACS.JPCLETT.1C01460

Similar

MEDLINE

...
LILACS

LIS


Full text: Available Collection: International databases Database: MEDLINE Main subject: Water / Viral Matrix Proteins / Molecular Dynamics Simulation / SARS-CoV-2 Type of study: Experimental Studies Limits: Humans Language: English Journal: J Phys Chem Lett Year: 2021 Document Type: Article Affiliation country: ACS.JPCLETT.1C01460