Slightly belated, these are our thoughts on the MABRA workshop at the University of Surrey, which five OPIGlegts attended in January 2020.
Category Archives: Protein Structure
The evolution of contact prediction – a new paper
I’m so pleased to be able to write about our work on The evolution of contact prediction: evidence that contact selection in statistical contact prediction is changing (Bioinformatics btz816). Contact prediction – the prediction of parts of the amino-acid chain that are close together – has been critical to improving the ability of scientists to predict protein structures over the last decade. Here we look at the properties of these predictions, and what that might mean for their use.
The paper begins with a question. If contact prediction methods are based on statistical properties of sequence alignments, and those alignments are generated in the presence of ecological and physical constraints, what effect do the physical constraints have on the statistical properties of real sequence alignments? More concisely: when we predict contacts, do we predict particularly important contacts?
Continue readingWhat are Hotspots in Structural Biology?
“Hotspot” is one of those extremely versatile words, similar to “model” and “buffer”, which can mean a variety of things depending on context. According to Merriam-Webster, a hotspot is “a place of more than usual interest, activity, or popularity”. This is the most general definition of the concept I could find in a quick search, and the one I find closest in spirit to the way hotspots are perceived in a structural biology context. What this blog post is definitely not about are hotspots as “areas of political, military, or civil unrest” (my experience with them has so far been mostly peaceful), or anything to do with geology, WiFi connections, or forest fires.
However, even within the context of structural biology and structure-based drug design, the word “hotspot” has multiple meanings. In this blog post, I will try to summarise the main ones I have come across, the (sometimes subtle) differences between them, and provide a few useful papers to serve as an entry point for interested readers. Continue reading
Comparative analysis of the CDR loops of antigen receptors
Allow me to present our recently accepted paper: Comparative analysis of the CDR loops of antigen receptors, to appear in Frontiers in Immunology [1]. In the blog post I will give a quick five-minute summary of the key messages in this work.
Continue readingA collection of prion factoids
It’s been several years since I last presented a talk on prions to OPIG, so I thought a neat way of getting up to date would be to read “The prion 2018 round tables“. What’s the current understanding and are we any closer to determining a structure of PrPSc?
Continue readingTwo Tools for Systematically Compiling Ensembles of Protein Structures
In order to know how a protein works, we generally want to know its 3-dimensional structure. We then can either try to solve it ourselves (which requires considerable time, skill, and resources), or look for it in the Protein Data Bank, in case it has already been solved. The vast majority of structures in the Protein Data Bank (PDB) are solved through protein crystallography, and represent a “snapshot” of the conformational space available to our protein of interest. Continue reading
How to Iterate in PyMOL
Sometimes pointing-and-clicking just doesn’t cut it. With PyMOL’s built-in Python interpreter, repetitive actions are made simple.
Continue readingWhich fragment first?
Crystallographic fragment based lead discovery is a now a routine technique, which can sample 1000’s of compounds per week. But how do we identify the most appropriate compounds to screen against our target of interest?
Continue readingModelling Conformational Flexibility of Kinases in Inactive States
I would like to shamelessly advertise my master thesis project which just got published in Proteins. Keep on reading if you are interested in kinases and/or systematic modelling of protein families.
Continue readingWhat is the hydrophobic-polar (HP) model?
Proteins are fascinating. They are ubiquitous in living organisms, carrying out all kinds of functions: from structural support to unbelievably powerful catalysis. And yet, despite their ubiquity, we are still bemused by their functioning, not to mention by how they came to be. As computational scientists, our research at OPIG is mostly about modelling proteins in different forms. We are a very heterogeneous group that leverages approaches of diverse scale: from modelling proteins as nodes in a complex interaction network, to full atomistic models that help us understand how they behave.
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