Ruchi’s paper “Sequence Specificity Despite Intrinsic Disorder : How a Disease-Associated Val/Met Polymorphism Rearranges Tertiary Interactions in a Long Disordered Protein” was just published in PLOS Computational Biology! This paper focuses on a common variation in Brain-derived Neurotrophic Factor (BDNF). About 70% of the US population has two copies of the “V” form of the protein, 25% has one copy of the “V” form and one copy of the “M” form, and 5% has two copies of the “M” form. The particular copies you have can affect how you store memories and respond to stress.
The region of the protein containing the variant is disordered, and normally we would expect the “V” and “M” forms to behave very similarly. It was unclear why this small change would make any difference at all. In this paper we found that although the two forms do interact similarly with water, the “M” form (on the right) introduces a specific “Met-Met” interaction. We often don’t consider Met-Met interactions, even though they are common in structured proteins. Here we showed that they can also affect the behavior of disordered proteins, which in turn contributes to the natural variation among human brains.
Ruchi successfully defended her PhD thesis “Predicting the effect of genetic variance on the sequence-ensemble relationship of intrinsically disordered proteins.” Ruchi’s thesis used techniques ranging from sophisticated simulations requiring millions of supercomputing hours, to bioinformatics surveys of thousands of proteins.
During her thesis, Ruchi produced thousands of plots, diagrams, and figures in an effort to understand why a seemingly subtle change can have substantial effects. Then she did much harder work: left most of these figures on her hard-drive, and selected a compelling few that revealed a very cool scientific story. Congratulations, Ruchi!
A paper resulting from a collaboration between the Brannigan group and the Joseph Martin group in Rutgers-Camden Biology has just been published! “L-3,3’,5-triiodothyronine and pregnenolone sulfate inhibit Torpedo nicotinic acetylcholine receptors” is primarily an experimental paper that tests hypotheses about how the electrostatic charge of hormones changes their effects on acetylcholine receptors.
Understanding this information helps clarify why certain molecules bind to these receptors and others don’t, which is important for designing new molecules like drugs.
The study takes advantage of a very convenient property of thyroid hormone: thyroid hormone changes its charge (or protonation state) with a very slight decrease in physiological pH. The experiments were mainly carried out by Steven Moffett, a PhD student in the Martin Lab. Congratulations Steve!