Homology Modeling and Binding Site Analysis of SARS-CoV-2 (COVID-19) Main Protease 3D Structure

Homology Modeling and Binding Site Analysis of SARS-CoV-2 (COVID-19) Main Protease 3D Structure

Marion Olubunmi Adebiyi, Ibidun Christiana Obagbuwa
Copyright: © 2024 |Pages: 15
DOI: 10.4018/979-8-3693-3026-5.ch038
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Abstract

The severe acute respiratory syndrome coronavirus 2 (SAR-Cov-2) caused the coronavirus (COVID-19) pandemic. The global concern is the discovery of a new target drug for the total cure. Recently, some research showed that a few COVID-19 enzymes may have been contemplated to be potential drug targets, but not much is known about its structural biology. This research investigates the 3-D structure of protease SAR-CoV-2. The tertiary structure was determined by homology modeling. The Swiss-Model workspace and the basic local alignment search tool (BLAST) were employed for modeling, and the resulted model was validated with programs that include PROCHECK, Verify3D, and QMEAN to ascertain reliability. To establish the structures that fitted, HHBlits software was employed. To verify the structure quality, a Ramachandran plot was exploited. The binding site was determined using CASTp and DeepSite algorithms, which showed that this protein can be exploited as a prospective pharmaceutical target. Albeit further experimentation is required as a COVID-19 virus vaccine-design/target-drug.
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2. Materials And Methods

2.1 Computational Methods

The 3D modeling computational methods embroiled template selection, template alignment with the target, building model, and structure evolution. SARS-CoV-2 Main Protease sequence was fetched from the protein database (PDB) (Guenther et al.)- https://rcsb.org/structure/6ynq.

2.2. Searching for Template

BLAST and HHBlits were used for template searching in conjunction with the SWISS-MODEL template library (SMTL, last update: 2020-11-11, last included PDB release: 2020-11-06).

BLAST was engaged for the search for target sequence with the content of Amino acids in the SMTL and found 165 templates. The procedures listed in (Steinegger et al.) were used to build the initial HHblists profile, followed by one iteration of HHblits against Uniclust30 (von den Driesch et al.). The obtained profile has then been searched against all profiles of the SMTL. A total of 480 templates were found.

2.3 Template Selection and Sequence Alignment

The basic local alignment tool (BLAST) server was used to thoroughly examined the protein data bank (PDB) and the UniProt Knowledgebase (UniProtKB)-accession number: P0DTD1 to discover the similar homologs of the sequence being enquired. 6YNQ_1|Chain A|Replicase polyprotein 1ab|severe acute respiratory syndrome coronavirus 2 (2697049) with RID (VP2K8RUB01R) carried out, and the discovered best template has accession number QOQ24800.1 (Stephen et al., 1997). The template quality was predicted from target template alignment features, and the highest quality template was selected for building the model.

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