Integrating single-molecule spectroscopy and simulations for the study of intrinsically disordered proteins

Over the last two decades, intrinsically disordered proteins and protein regions (IDRs) have emerged from a niche corner of biophysics to be recognized as essential drivers of cellular function. Various techniques have provided fundamental insight into the function and dysfunction of IDRs. Among these techniques, singlemolecule fluorescence spectroscopy and molecular simulations have played a major role in shaping our modern understanding of the sequence-encoded conformational behavior of disordered proteins. While both techniques are frequently used in isolation, when combined they offer synergistic and complementary information that can help uncover complex molecular details. Here we offer an overview of single-molecule fluorescence spectroscopy and molecular simulations in the context of studying disordered proteins. We discuss the various means in which simulations and single-molecule spectroscopy can be integrated, and consider a number of studies in which this integration has uncovered biological and biophysical mechanisms.

Automated summary

Over the past two decades, intrinsically disordered proteins and protein regions have been recognized as essential drivers of cellular function, with singlemolecule fluorescence spectroscopy and molecular simulations providing insight into their behavior. When combined, these techniques offer complementary information that can help uncover complex molecular details.