DOI: 10.15125/bath-00772
title: Dataset for "Rigidity, normal modes and flexible motion of a SARS-CoV-2 (COVID19) protease structure"

description: This file contains simulations and analysis carried out on two protein structures from the SARS-CoV-2 (COVID19) virus. These structures are PDB entries 6Y2E and 6LU7. Both structures represent the same homodimeric protease. 6Y2E represents the free protease while 6LU7 includes a bound inhibitor, N3.

The folder for each structure includes README files at each level describing how the structure has been processed and what results have been produced. This study includes rigidity analysis of the crystal structures, elastic network modelling to identify normal modes of the structures, and all-atom geometric simulations of flexible motion along normal mode directions. This study makes use of the PDB, the MolProbity structure processing webserver, FIRST rigidity analysis software, the FRODA geometric simulation engine, Elnemo elastic network modelling software, and PyMOL visualisation software. The SBFIRST code for identication of covalent and noncovalent interactions in a protein structure is included in this collection of data.
description: Input data: PDB entries 6Y2E and 6LU7
description: Analysis and processing workflow for 6LU7 is described here. The procedure for 6Y2E was essentially identical.

Downloaded from PDB repository.
Note that this structure contains the protease structure as chain A and an inhibitor as chain C.
Opened in PyMOL v0.99.
Symmetry applied; symmetry mate selected to form homodimeric structure; symmetry mate chain reset to B; symmetry mate of inhibitor chain reset to D; homodimer saved including inhibitors.
Homodimer processed using the MolProbity website to add hydrogens at electron-cloud positions, including flipping of ambiguous residues where suggested.
Hydrogenated homodimer opened in PyMOL v0.99; heteroatoms, mostly water residues, removed, but inhibitor retained; alternative side chain configurations removed; structure saved as "6lu7inhib.pdb".`

Covalent, hydrogen-bond and hydrophobic interactions identified based on structure geometry and saved in files cov.in, hbonds.in, hphobes.in. hphobes.in has been edited to remove a phobic tether linking ALA285 of each chain and tethers linking LEU286 of one chain to THR280 of the other, as examination of the structure suggested that these tethers were not appropriate as a permanent constraint in the system. This bond analysis was carried out using the SBFIRST utility, a copy of which is included with this data set. The .in files are suitable for use as input to the rigidity analysis software FIRST, from Arizona State University. The stacked.in file is empty (would hold stacked-ring interactions in nucleic acid structures).

Static rigidity analysis of the structure is carried out in the folder Clusters. Normal mode analysis identifying nontrivial low-frequency modes intrinsic to the structure is carried out in the folder Modes. Geometric simulations of flexible motion along the normal mode directions is carried out in the folder Runs, controlled by the bash script file loopFRODA.sh.
description: The Elnemo elastic network structure software is available online from http://www.sciences.univ-nantes.fr/elnemo/

The FIRST rigidity analysis software, including the FRODA geometric simulation engine, should be available from flexweb.asu.edu. If there are difficulties obtaining the software from this source, please contact Dr. Stephen Wells (saw42@bath.ac.uk) who can provide a copy of FIRST for academic users.

The SBFIRST code for identication of covalent and noncovalent interactions in a protein structure is included in this collection of data.

The Elnemo website includes comprehensive citations for the Elnemo elastic network method and software. The primary citation for the SBFIRST identification of interactions is DOI:10.1088/1478-3975/ab2b5c (MacManus, Wells, Walker 2019). The primary citation for the use of Elnemo/FIRST/FRODA in combination is DOI:10.1088/1478-3975/9/1/016008 (Jimenez-Roldan, Freedman, Roemer, Wells 2012) and a detailed discussion of the method can be found as DOI:10.1007/978-1-62703-658-0_10 (Wells 2014). The primary citation for the FRODA geometric simulation engine is DOI:10.1088/1478-3975/2/4/S07 (Wells, Menor, Hespenheide, Thorpe 2005). The primary citation for the FIRST rigidity analysis software is DOI:10.1002/prot.1081 (Jacobs, Rader, Kuhn, Thorpe 2001).
description: A folder for each protein structure contains subfolders for Clusters (containing static rigidity analysis), Modes (elastic network modelling) and Runs (geometric simulations of flexible motion). README files in each folder and subfolder provide additional details.