How to assess the structural dynamics of transcription factors by integrating sparse NMR and EPR constraints with molecular dynamics simulations

We review recent advances in modeling structural ensembles of transcription factors from nuclear magnetic resonance (NMR) and electron paramagnetic resonance (EPR) spectroscopic data, integrated with molecular dynamics (MD) simulations. We focus on approaches that confirm computed conformational ensembles by sparse constraints obtained from magnetic resonance. This combination enables the deduction of functional and structural protein models even if nuclear Overhauser effects (NOEs) are too scarce for conventional structure determination. We highlight recent insights into the folding-upon-DNA bind -ing transitions of intrinsically disordered transcription factors that could be assessed using such integra-tive approaches. (C) 2021 The Author(s). Published by Elsevier B.V. on behalf of Research Network of Computational and Structural Biotechnology.

Automated summary

This review discusses recent advances in modeling structural ensembles of transcription factors using NMR and EPR spectroscopic data integrated with MD simulations. The focus is on approaches that confirm computed conformational ensembles by sparse constraints obtained from magnetic resonance. Recent insights into the folding-upon-DNA binding transitions of intrinsically disordered transcription factors using integrative approaches are highlighted.