scholarly journals Interfacial Water Many-Body Effects Drive Structural Dynamics and Allosteric Interactions in SARS-CoV-2 Main Protease Dimerization Interface

2021 ◽  
pp. 6218-6226
Author(s):  
Dina El Ahdab ◽  
Louis Lagardère ◽  
Théo Jaffrelot Inizan ◽  
Fréderic Célerse ◽  
Chengwen Liu ◽  
...  
Keyword(s):  
Structural Dynamics ◽  
Interfacial Water ◽  
Many Body ◽  
Allosteric Interactions ◽  
Main Protease ◽  
Dimerization Interface ◽  
Many Body Effects

scholarly journals Interfacial Water Many-body Effects Drive Structural Dynamics and Allosteric interactions in SARS-CoV-2 Main Protease Dimerization Interface

2021 ◽  
Author(s):  
Dina El Ahdab ◽  
Louis Lagardère ◽  
Theo Jaffrelot Inizan ◽  
Frédéric Célerse ◽  
Chengwen Liu ◽  
...  
Keyword(s):  
Structural Dynamics ◽  
Adaptive Sampling ◽  
Many Body ◽  
Allosteric Site ◽  
Allosteric Interactions ◽  
Main Protease ◽  
Dimerization Interface ◽  
Bond Network ◽  
Dynamics Simulations ◽  
Many Body Interactions

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 microseconds) using the AMOEBA polarizable force field (PFF). This interface is structured by a complex H-bond network that is only stable 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, since they are connected to the global interface H-bond network and able to adapt their dipole moment (and dynamics) to their diverse local physico-chemical micro-environments. The water-interface many-body interactions appear to drive the interface volume fluctuations and to therefore mediate the allosteric interactions with the catalytic cavity.

scholarly journals Interfacial Water Many-body Effects Drive Structural Dynamics and Allosteric interactions in SARS-CoV-2 Main Protease Dimerization Interface

2021 ◽  
Author(s):  
Dina El Ahdab ◽  
Louis Lagardère ◽  
Theo Jaffrelot Inizan ◽  
Frédéric Célerse ◽  
Chengwen Liu ◽  
...  
Keyword(s):  
Structural Dynamics ◽  
Adaptive Sampling ◽  
Many Body ◽  
Allosteric Site ◽  
Allosteric Interactions ◽  
Main Protease ◽  
Dimerization Interface ◽  
Bond Network ◽  
Dynamics Simulations ◽  
Many Body Interactions

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 microseconds) using the AMOEBA polarizable force field (PFF). This interface is structured by a complex H-bond network that is only stable 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, since they are connected to the global interface H-bond network and able to adapt their dipole moment (and dynamics) to their diverse local physico-chemical micro-environments. The water-interface many-body interactions appear to drive the interface volume fluctuations and to therefore mediate the allosteric interactions with the catalytic cavity.

scholarly journals Interfacial Water Many-body Effects Drive Structural Dynamics and Allosteric interactions in SARS-CoV-2 Main Protease Dimerization Interface

2021 ◽  
Author(s):  
Dina El Ahdab ◽  
Louis Lagardère ◽  
Theo Jaffrelot Inizan ◽  
Frédéric Célerse ◽  
Chengwen Liu ◽  
...  
Keyword(s):  
Structural Dynamics ◽  
Adaptive Sampling ◽  
Many Body ◽  
Allosteric Site ◽  
Allosteric Interactions ◽  
Main Protease ◽  
Dimerization Interface ◽  
Bond Network ◽  
Dynamics Simulations ◽  
Many Body Interactions

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 microseconds) using the AMOEBA polarizable force field (PFF). This interface is structured by a complex H-bond network that is only stable 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, since they are connected to the global interface H-bond network and able to adapt their dipole moment (and dynamics) to their diverse local physico-chemical micro-environments. The water-interface many-body interactions appear to drive the interface volume fluctuations and to therefore mediate the allosteric interactions with the catalytic cavity.

Gain characteristics of GaN quantum wells including many body effects

1995 ◽  
Vol 31 (14) ◽  
pp. 1149 ◽  
Author(s):  
P. Rees ◽  
C. Cooper ◽  
P. Blood ◽  
P.M. Smowton ◽  
J. Hegarty
Keyword(s):  
Quantum Wells ◽  
Many Body ◽  
Many Body Effects

scholarly journals High-resolution mining of the SARS-CoV-2 main protease conformational space: supercomputer-driven unsupervised adaptive sampling

2021 ◽  
Author(s):  
Théo Jaffrelot Inizan ◽  
Frédéric Célerse ◽  
Olivier Adjoua ◽  
Dina El Ahdab ◽  
Luc-Henri Jolly ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
High Resolution ◽  
Adaptive Sampling ◽  
Force Fields ◽  
Sampling Strategy ◽  
Md Simulations ◽  
Conformational Space ◽  
Many Body ◽  
Polarizable Force Fields ◽  
Main Protease

We provide an unsupervised adaptive sampling strategy capable of producing μs-timescale molecular dynamics (MD) simulations of large biosystems using many-body polarizable force fields (PFFs).

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