Fast assessment of human receptor-binding capability of 2019 novel coronavirus (2019-nCoV)

Qiang Huang; Andreas Herrmann

Because the 2019-nCoVgenome has just been sequenced for a very short period of time, an experimental 3D structure for performing protein-protein docking of 2019-nCoV S-RBD to ACE2 is not yet available. Alternatively, computational methods may be used to predict the 3D structure (Schwede et al., 2009) . Fortunately, the 2019-nCoV genome has shown that the amino-acid . CC-BY-NC-ND 4.0 International license author/funder. It is made available under a The copyright holder for this preprint (which was not peer-reviewed) is the . https://doi.org/10.1101/2020.02.01.930537 doi: bioRxiv preprint 6 sequence of the S-protein is about 75% identical to that of the SARS-CoV S-protein ( Fig. 2A) . Therefore, with the SARS-CoV S-RBD structure as a template, it is possible to use high-resolution homology modeling method to accurately predict the 3D model (Qian et al., 2007) . To the end, we first generated an initial model for the 2019-nCoV S-RBD via SWISS-MDOEL server at https://swissmodel.expasy.org, with the experimental S-RBD structure of SARS-CoV as the template (PDB 2AJF). Then, we performed all-atom refinements to optimize this initial model with Rosetta protocols (see Methods). The top-1 scoring model was used as the 3D structure of the 2019-nCoV S-RBD for the protein-protein docking with the experimental structure of ACE2 from PDB . CC-BY-NC-ND 4.0 International license author/funder. It is made available under a The copyright holder for this preprint (which was not peer-reviewed) is the . https://doi.org/10.1101/2020.02.01.930537 doi: bioRxiv preprint 7 2AJF. By superimposing this model onto the SARS-CoV S-RBD structure (Fig. 2B) , we obtained the starting configuration of S-RBD complexed with ACE2 for the 2019-nCoV docking (Fig. 2C) . From this complex, we found that most of the residues that are different from those of SARS-CoV S-RBD are close to or located in the binding interface. No doubt, such a structural distribution of the residues could lead to a different binding affinity from that of SARS-CoV S-RBD binding to ACE2.