MMGB/SA Consensus Estimate of the Binding Free Energy Between the Novel Coronavirus Spike Protein to the Human ACE2 Receptor

BioRxiv : the Preprint Server for Biology
Negin Forouzesh, Alexey V Onufriev

Abstract

The ability to estimate protein-protein binding free energy in a computationally efficient via a physics-based approach is beneficial to research focused on the mechanism of viruses binding to their target proteins. Implicit solvation methodology may be particularly useful in the early stages of such research, as it can offer valuable insights into the binding process, quickly. Here we evaluate the potential of the related molecular mechanics generalized Born surface area (MMGB/SA) approach to estimate the binding free energy {Delta}Gbind between the SARS-CoV-2 spike receptor-binding domain and the human ACE2 receptor. The calculations are based on a recent flavor of the generalized Born model, GBNSR6. Two estimates of {Delta}Gbind are performed: one based on standard bondi radii, and the other based on a newly developed set of atomic radii (OPT1), optimized specifically for protein-ligand binding. We take the average of the resulting two {Delta}Gbind values as the consensus estimate. For the well-studied Ras-Raf protein-protein complex, which has similar binding free energy to that of the SARS- CoV-2/ACE2 complex, the consensus {Delta}Gbind = -11.8 {+/-} 1 kcal/mol, vs. experimental -9.7 {+/-} 0.2 kcal/mol. The consensus estim...Continue Reading

Methods Mentioned

BETA
isothermal titration calorimetry
X-ray
surface plasmon resonance

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