ABSTRACT
The worldwide CoVid-19 pandemic has led to an unprecedented push across the whole of the scientific community to develop a potent antiviral drug and vaccine as soon as possible. Existing academic, governmental and industrial institutions and companies have engaged in large-scale screening of existing drugs, in vitro, in vivo and in silico. Here, we are using in silico modelling of SARS-CoV-2 drug targets, i.e. SARS-CoV-2 protein structures as deposited on the Protein Databank (PDB). We study their flexibility, rigidity and mobility, an important first step in trying to ascertain their dynamics for further drug-related docking studies. We are using a recent protein flexibility modelling approach, combining protein structural rigidity with possible motion consistent with chemical bonds and sterics. For example, for the SARS-CoV-2 spike protein in the open configuration, our method identifies a possible further opening and closing of the S1 subunit through movement of SB domain. With full structural information of this process available, docking studies with possible drug structures are then possible in silico. In our study, we present full results for the more than 200 thus far published SARS-CoV-2-related protein structures in the PDB.
Competing Interest Statement
The authors have declared no competing interest.
Footnotes
1 We expect to continue to increase the number of SARS-CoV-2-related proteins to be included in our study as more structures become available.
2 We use the term domain here to denote large regions of a protein connected in the same rigidity cluster. Usually, domains in a biological sense are also detected as domains in a rigidity sense as used here.32 However, this relationship is not necessarily always the case.
3 With nearly 3000 residues in the structure of the trimer, is it impossible to capture the behaviour in a single figure that at the same time would allow the reader to see enough detail. Nevertheless, we include the figure among the supplementary materials so that both an overview can be achieved as well as enough detail studied by using standard scalable postscript document viewers.
