Extracting the Causality of Correlated Motions from Molecular Dynamics Simulations

The information theory measure of transfer entropy is used to extract the causality of correlated motions from molecular dynamics simulations. For each pair of correlated residues, the method quantifies which residue drives the correlated motions, and which residue responds. The measure reveals how correlated motions are used to transmit information through the system, and helps to clarify the link between correlated motions and biological function in biomolecular systems. The method is illustrated by its application to the Ets-1 transcription factor, which partially unfolds upon binding DNA. The calculations show dramatic changes in the direction of information flow upon DNA binding, and elucidate how the presence of DNA is communicated from the DNA binding H1 and H3 helices to inhibitory helix HI-1. Helix H4 is shown to act as a relay, which is attenuated in the apo state.