TY - JOUR
T1 - Integrating single-molecule spectroscopy and simulations for the study of intrinsically disordered proteins
AU - Alston, Jhullian J.
AU - Soranno, Andrea
AU - Holehouse, Alex S.
N1 - Funding Information:
This work was supported by NIGMS R25 IMSD Training Grant GM103757 (J.J.A.), the Longer Life Foundation - RGA/Washington University Collaboration (A.S.H.) and the NIA AG062837 (A.S.).
Publisher Copyright:
© 2021 Elsevier Inc.
PY - 2021/9
Y1 - 2021/9
N2 - 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, single-molecule 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.
AB - 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, single-molecule 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.
KW - All-atom simulations
KW - FRET
KW - Fluorescence correlation spectroscopy
KW - Förster resonance energy transfer
KW - Intrinsically disordered proteins
KW - Molecular simulations
KW - Protein folding
KW - Single-molecule spectroscopy
KW - smFRET
UR - http://www.scopus.com/inward/record.url?scp=85104293164&partnerID=8YFLogxK
U2 - 10.1016/j.ymeth.2021.03.018
DO - 10.1016/j.ymeth.2021.03.018
M3 - Article
C2 - 33831596
AN - SCOPUS:85104293164
SN - 1046-2023
VL - 193
SP - 116
EP - 135
JO - Methods
JF - Methods
ER -