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.