Backbone free energy estimator, a new geometric tool in structural biology
Special IHES/MPIM colloquium Hydrogen bonds stabilize the 3-dimensional structures of most proteins. In the aqueous environment, they lie at the edge of stability and hence are easily formed and broken, especially those with high free energy. Using a Boltzmann-like formalism, empirical sampling of their geometry leads to free energy estimates, thus allowing a priori prediction of protein regions primed for structural rearrangement. One among diverse applications involves viral glycoproteins or capsids, namely those proteins employed by viruses to attach to and fuse with or penetrate the host cell. Here the methods are used to identify sites of interest for vaccine/drug/testing development, in particular for the SARS CoV-2 spike glycoprotein that causes COVID-19. All this will be explained from first principles.