Calculating the change in Gibbs free energy (ddGbind) of an improved alpha-ketoamide inhibitor binding associated with genetic variations of SARS-CoV-2 main protease – post18

Posted onAuthorSetayesh YazdaniLeave a comment

Since we posted our analysis of genetic variation of SARS-CoV-2 main protease (MPro) with inhibitor N3 (PDB: 7bqy), there have been other inhibitors co-crystallized with the MPro (PDB: 6lze, PDB: 6m0k, and PDB: 6y2f). In my last post, I talked about the two inhibitors, 11a and 11b (PDB: 6lze, PDB: 6m0k) and in today’s post, Read More …

Brachyury (TBXT) ligands for chordoma: 1. Fragment optimization strategy 2. fragment F9000505, B-site, PDB 5QRU

Posted onAuthorDavid DrewryLeave a comment

Introduction In this blog post I will share details on the new molecules we have designed and synthesized or purchased based on one of our original hits from the x-ray crystallography fragment screen. The compound is called F9000505 and it is bound to pocket B. The crystal structure was deposited in the Protein Data Bank Read More …

Electroporation: a second look

Posted onAuthorElizabeth BrownLeave a comment

It’s never too late to take another look at your data. The incredibly knowledgeable Sally Cowley suggested that I shouldn’t just think about how many cells contain any AlexFluor488 antibody after electroporation, but how bright each cell is (i.e. the amplitude of fluorescence). Looking at this instead will give me an idea of how much Read More …

Structure and X-ray Fragment screening of SARS-Cov-2 helicase (Nsp13)

Posted onAuthorJoseph NewmanLeave a comment

My name is Joseph Newman and I have been working in Lab of Opher Gileadi at SGC Oxford since 2013 mainly on targeting DNA repair factors as synthetic lethal targets for early stage development of new cancer therapeutics. Like many scientists my normal laboratory based research activities were disrupted by the lockdown, and when Opher Read More …

Back to SARS-CoV-2 Main Protease: Calculating the change in Gibbs free energy (ddGbind) of two peptidomimetic aldehyde Inhibitors binding associated with genetic variations of SARS-CoV-2 main protease – post17

Posted onAuthorSetayesh YazdaniLeave a comment

Since we posted our analysis of genetic variation of SARS-CoV-2 main protease (MPro) with inhibitor N3 (PDB: 7bqy), there have been other inhibitors co-crystallized with the MPro (PDB: 6lze and PDB: 6m0k). MPro acts like a scissor by cutting SARS-CoV-2 polyproteins into functional pieces, making it a critical target for antiviral therapies against SARS-CoV-2. In Read More …

Generation of stable mammalian cell lines for the expression of proteins related to COVID-19 through random integration

Posted onAuthorJong FuLeave a comment

Background: Scientists centred around University of Oxford came together in the current COVID-19 pandemic to contribute to relevant studies collaboratively. Researchers with no prior experience in virology studies, myself included, had volunteered our time to contribute whichever way we can based on our field of expertise. The Biotech team of SGC Oxford, headed by Nicola Read More …

Predicting the effect of all possible mutations at nsp3-Mac1 ADPr-binding site on ADPr binding – Post 16

Posted onAuthorSetayesh YazdaniLeave a comment

In my last post, I showed you the genetic variants at the ADP-ribose (ADPr) binding site of SARS-CoV-2 nsp3-Mac1 and the predicted effects of those mutations on ADPr binding with Mac1. Next, we wanted to assess the effect of all possible mutations at the sidechains lining the ADPr binding site of nsp3-Mac1 and how that Read More …

Genetic variability at the ADP-ribose Binding Site of the SARS-CoV-2 nsp3-Mac1 and predicted effects of mutations on ADP-ribose binding – Post 15

Posted onAuthorSetayesh YazdaniLeave a comment

In two of my previous posts 13 and 14, I showed how we found the residues lining the ADP ribose (ADPr) binding site of SARS-CoV-2 nsp3-Mac1 and we looked at the variability of this site across Alpha- and Betacoronavirus entries from UniProt. In addition to the UniPro sequences, we were interested in looking at variants Read More …

Mapping the genetic variations of Alpha- and Betacoronavirus UniProt entries onto SARS-CoV-2 nsp3-Mac1 crystal structure – Post 14

Posted onAuthorSetayesh YazdaniLeave a comment

In my last post, I showed how we found the residues lining the ADP-ribose (ADPr) binding site of SARS-CoV-2 nsp3-Mac1 using its crystal structure (PDB: 6w02). In this post, I will show the sequence diversity across UniProt entries from the Alpha- and Betacoronavirus genera and map that to the Mac1’s ADPr binding site using the Read More …

WDR5 and histone H3 interaction cell assay report

Posted onAuthorMagdalena SzewczykLeave a comment

  Background WDR5 belongs to the WD-repeat protein family and is an important component of various complexes, including SET1/MLL, NuRD, and NSL complex. It interacts with several binding partners via the “WDR5-interacting” (Win) site (e.g. symmetrically dimethylated histone H3R2, MLL1-4, SET1-2) or “WDR5-binding motif” (WBM) site (e.g. c,l,n-MYC, RBBP5). WDR5 emerged as a prime target Read More …