A couple of weeks ago I was lucky enough to be asked to speak at the 5th Computational Drug Discovery & Development for Biologics Summit. This was my first virtual conference – it was a shame I didn’t get to visit Boston, and presenting to my empty room was slightly bizarre, but it was great to hear what people have been working on, and there’s definitely something to be said for attending a conference in fluffy socks…
In my work, I mainly look at antigen-bound antibodies and this means a lot of analysing interfaces. Specifically, I spend a lot of my time examining the contributions of complementarity-determining regions (CDRs) to antigen binding, but what about antibodies where the framework (FW) region also contributes to binding? Such structures do exist, and these interactions are rarely trivial. As such, a recent preprint I came across where the authors examined the DE loops of antibodies was a great motivator to broaden my horizons!
Continue readingIn the past few months we have seen a lot of papers reporting antibodies that they found to bind to SARS-CoV-2 (a database can be found here: http://opig.stats.ox.ac.uk/webapps/covabdab/). Some of them were from the analysis of a patient’s immune system. Some of them come with crystal structures to show where they bind. Some don’t have structures, but they have the sequences and some competition assay data to show approximately where on the spike protein they bind. The main focus is around an area called the Receptor Binding Domain (RBD) which is where the spike protein engages the human ACE2 receptor and causes the downstream problems. In this paper, the authors ran a complete mutagenesis on the RBD of the SARS-CoV-2 spike protein.
Continue readingSince my last blogpost on this topic back in 2018, OPIG has expanded its range of tools for antibody/BCR analysis. Here is an updated summary of the OPIG antibody databases and immunoinformatics tools.
Continue readingHello,
Today is the day for my final blog post before I enter a thesis writing mode. Using this given opportunity, I would like to present to you our recent update to the Observed Antibody Space (OAS) resource where we included paired antibody data (http://opig.stats.ox.ac.uk/webapps/oas).
Continue readingI came across a recent paper on the antibody-protein binding and conformational changes. As I work mainly on the binding site/Fv regions of antibodies, I am intrigued to see the role of the constant domains in the overall antibody function.
Continue readingThis blog post finally combines the two great passions of my life: antibodies and dogs. Therapeutic antibody development is a huge area and is certainly not limited to humans. In the process of developing antibodies, we often use mouse or rat antibodies, obtained by injecting the animal with the antigen of choice and then collecting the resulting antibodies. The first monoclonal antibodies (mAbs) were produced in this way, by fusing spleen B cells from an immunised mouse or rabbit with immortalised myeloma cells to form antibody-expressing hybridoma cells. However, using antibodies to treat disease in animals lags behind humans.
Continue readingI have an unconscious habit of personification, and I always see the antibody light chain as lazy for not contributing more residues to binding interfaces (obviously a generalisation – e.g. insertions in CDRL4 in anti-HIV bNAbs [1]). Perhaps this is why I have a personal preference for the more diverse [2] heavy chain with its specificity-determining [3] CDR3. Having written this down, I realised it’s actually pretty weird to consider an antibody chain as a person and I ought to re-educate myself about the role that light chains play.
Continue readingAt group meeting a few weeks ago I presented this paper, “Landscape of Non-canonical Cysteines in Human VH Repertoire Revealed by Immunogenetic Analysis“, from Prabakaran and Chowdhury. The paper is an investigation of the frequency, location and patterns of cysteines contained in human antibody sequences. Cysteines are important amino acids found in proteins, including antibodies, which can form disulphide bonds with other cysteines due to the presence of their reactive sulfhydryl group in the side chain.
Continue readingToday is the day for another (potentially penultimate) blog post from me. Using this opportunity, I would like to introduce to you our recent update to the Observed Antibody Space (OAS) resource.
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