Identification of novel mutations in SARS-COV-2 isolates from Turkey.
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ABSTRACT:
SUBMITTER: Rehman S
PROVIDER: S-EPMC7538173 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:SARS-CoV-2 inherits a high rate of mutations making it better suited to the host since its fundamental role in evolution is to provide diversity into the genome. This research aims to identify variations in Turkish isolates and predict their impacts on proteins. To identify novel variations and predict their impacts on protein dynamics, in silico methodology was used. The 411 sequences from Turkey were analysed. Secondary structure prediction by Garnier-Osguthorpe-Robson (GOR) was used. To find the effects of identified Spike mutations on protein dynamics, the SARS-CoV-2 structures (PDB:6VYB, 6M0J) were uploaded and predicted by Cutoff Scanning Matrix (mCSM), DynaMut and MutaBind2. To understand the effects of these mutations on Spike protein molecular dynamics (MD) simulation was employed. Turkish sequences were aligned with sequences worldwide by MUSCLE, and phylogenetic analysis was performed via MegaX. The 13 novel mutations were identified, and six of them belong to spike glycoprotein. Ten of these variations revealed alteration in the secondary structure of the protein. Differences of free energy between the reference sequence and six mutants were found below zero for each of six isolates, demonstrating these variations have stabilizing effects on protein structure. Differences in vibrational entropy calculation revealed that three variants have rigidification, while the other three have a flexibility effect. MD simulation revealed that point mutations in spike glycoprotein and RBD:ACE-2 complex cause changes in protein dynamics compared to the wild-type, suggesting possible alterations in binding affinity. The phylogenetic analysis showed Turkish sequences distributed throughout the tree, revealing multiple entrances to Turkey.
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