Evolutionary dynamics of the protein structure-function relation and the origin of the genetic code

Gustavo Caetano-Anolles, University of Illinois at Urbana-Champaign

Usage Details

The molecular functions of proteins are considered the result of the structural diversity and flexibility of protein loops. Protein flexibility has been thought to be a vital component in shaping the origin of the genetic code, the history of which is intertwined with that of aminoacyl-tRNA synthetase enzymes and the dipeptide composition of proteins. However, the connection between protein structure and function is poorly understood. In a previous Blue Waters allocation we acquired unprecedented atomistic details of the dynamics of selected loop regions in these synthetase enzymes. Here we aim to study the structure-function connection with microsecond-scale molecular dynamic simulations of the entire repertoire of loop regions of the enzymes using the NAMD 2.9 platform and CHARMM36 force field. This study will provide important insight into how the biophysics of protein structure harbors evolutionary signal and conditions the associated protein function. Our study also aims to identify structural motions important to the functionality of a protein with the help of a "structural alphabet" derived using machine learning methods.