4 December 2020
Hashim Al-Hashimi
Duke University School of Medicine and
Duke Center for RNA Biology
At the most fundamental level, living organisms are the product of biomolecules interacting with one another through a process commonly referred to as molecular recognition. To understand how biomolecule interact with one another, we need a framework that describes those properties of the biomolecules that determine their binding affinities and specificities. Our current understanding dates back six decades ago when Linus Pauling proposed that specificity is achieved through the structural complementarity of the binding partners. This concept has been reinforced over the decades thanks to advances in the determination of high-resolution structures of biomolecules by X-ray crystallography and cryoEM. Static structures only carry information regarding one half of the molecular recognition equation, which I will refer to as income. This half describes the favorable contacts formed upon complex formation. The second half, which has received much less attention, I will refer to as income tax. It represents the energetic cost associated with changing the structure of a biomolecule from one form to another when binding a partner molecule. Unlike income, the income tax half of the molecular recognition equation can only be determined experimentally through an ensemble description of biomolecules as a probability distribution of many different conformations. I will argue that income tax, and mechanisms for tax evasion, are ubiquitous in biology and disease, drawing on DNA replication as a primary example.