Selected article for: "computational analysis and detailed analysis"

Author: Ramos-Guzmán, Carlos A; Ruiz-Pernía, J Javier; Tuñón, Iñaki
Title: Computational simulations on the binding and reactivity of a nitrile inhibitor of the SARS-CoV-2 main protease
  • Cord-id: 15epxrd6
  • Document date: 2021_1_1
  • ID: 15epxrd6
    Snippet: We present a detailed computational analysis of the binding mode and reactivity of the novel oral inhibitor PF-07321332 developed against the SARS-CoV-2 3CL protease. Alchemical free energy calculations suggest that positions P3 and P4 could be susceptible to improvement in order to get a larger binding strength. QM/MM simulations unveil the reaction mechanism for covalent inhibition, showing that the nitrile warhead facilitates the recruitment of a water molecule for the proton transfer step.
    Document: We present a detailed computational analysis of the binding mode and reactivity of the novel oral inhibitor PF-07321332 developed against the SARS-CoV-2 3CL protease. Alchemical free energy calculations suggest that positions P3 and P4 could be susceptible to improvement in order to get a larger binding strength. QM/MM simulations unveil the reaction mechanism for covalent inhibition, showing that the nitrile warhead facilitates the recruitment of a water molecule for the proton transfer step.

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