Covid‐19.bioreproducibility.org: A web resource for SARS‐CoV‐2‐related structural models

Abstract

The COVID‐19 pandemic has triggered numerous scientific activities aimed at understanding the SARS‐CoV‐2 virus and ultimately developing treatments. Structural biologists have already determined hundreds of experimental X‐ray, cryo‐EM, and NMR structures of proteins and nucleic acids related to this coronavirus, and this number is still growing. To help biomedical researchers, who may not necessarily be experts in structural biology, navigate through the flood of structural models, we have created an online resource, covid19.bioreproducibility.org, that aggregates expert‐verified information about SARS‐CoV‐2‐related macromolecular models. In this paper, we describe this web resource along with the suite of tools and methodologies used for assessing the structures presented therein. This article is protected by copyright. All rights reserved.

Crystallographic models of SARS-CoV-2 3CLpro: in-depth assessment of structure quality and validation

“…The final structures (some of which had to be further refined) were deposited in the database at https://covid-19. bioreproducibility.org (Brzezinski et al, 2021).…”

“…There have been specific campaigns to validate and correct PDB models of medicinally important drug-design targets, for instance metallo--lactamases (Raczynska et al, 2018) or proteins that bind cisplatin (Shabalin et al, 2015). The analysis, verification and improvement (if necessary) of all crystal structures of SARS-CoV-2 proteins is already the subject of an ongoing project (Wlodawer et al, 2020;Brzezinski et al, 2021), but without a dedicated overview and comparison of different structures. It is our aim to present here such a detailed analysis for 3CL pro that may be useful not only for this particular protein target but also to guide any future projects aimed at the interpretation of multiple structures of medicinally important macromolecules.…”

Rapid response to emerging biomedical challenges and threats

“…The criteria that we use to evaluate each structure result from experience acquired over several such projects and are relatively straightforward. They were previously described in the paper introducing the https://covid-19.bioreproducibility.org server (Brzezinski et al, 2021), as well as in several papers published on this subject (Wlodawer et al, 2013;Shabalin et al, 2015;Minor et al, 2016;Zheng et al, 2014). For convenience, we broadly classified the issues noticed in structures into three categories: minimal, moderate and significant.…”

“…Accordingly, several projects were initiated to assess the SARS-CoV-2 structures (Wlodawer et al, 2020;Croll et al, 2020), in addition to previously established structure rerefinement resources such as PDB-REDO (Touw et al, 2016). These efforts resulted in the creation of web servers, for example https://covid-19.bioreproducibility.org, that are meant to organize the workflow and make the results more easily digestible to the biological and medicinal communities (Brzezinski et al, 2021).…”

“…With an accumulation of structures to validate and possibly re-model, re-refine and re-deposit, we decided to create an automatic tool to generate a report for each structure (Brzezinski et al, 2021) that goes beyond the validation report provided by the PDB. Our aim was to rapidly evaluate which cases need to be manually inspected and possibly corrected.…”