Interaction networks in protein folding via atomic-resolution experiments and long-time-scale molecular dynamics simulations

TY - JOUR

T1 - Interaction networks in protein folding via atomic-resolution experiments and long-time-scale molecular dynamics simulations

AU - Sborgi, Lorenzo

AU - Verma, Abhinav

AU - Piana, Stefano

AU - Lindorff-Larsen, Kresten

AU - Cerminara, Michele

AU - Santiveri, Clara M.

AU - Shaw, David E.

AU - De Alba, Eva

AU - Muñoz, Victor

PY - 2015

Y1 - 2015

N2 - The integration of atomic-resolution experimental and computational methods offers the potential for elucidating key aspects of protein folding that are not revealed by either approach alone. Here, we combine equilibrium NMR measurements of thermal unfolding and long molecular dynamics simulations to investigate the folding of gpW, a protein with two-state-like, fast folding dynamics and cooperative equilibrium unfolding behavior. Experiments and simulations expose a remarkably complex pattern of structural changes that occur at the atomic level and from which the detailed network of residue-residue couplings associated with cooperative folding emerges. Such thermodynamic residue-residue couplings appear to be linked to the order of mechanistically significant events that take place during the folding process. Our results on gpW indicate that the methods employed in this study are likely to prove broadly applicable to the fine analysis of folding mechanisms in fast folding proteins. (Figure Presented).

AB - The integration of atomic-resolution experimental and computational methods offers the potential for elucidating key aspects of protein folding that are not revealed by either approach alone. Here, we combine equilibrium NMR measurements of thermal unfolding and long molecular dynamics simulations to investigate the folding of gpW, a protein with two-state-like, fast folding dynamics and cooperative equilibrium unfolding behavior. Experiments and simulations expose a remarkably complex pattern of structural changes that occur at the atomic level and from which the detailed network of residue-residue couplings associated with cooperative folding emerges. Such thermodynamic residue-residue couplings appear to be linked to the order of mechanistically significant events that take place during the folding process. Our results on gpW indicate that the methods employed in this study are likely to prove broadly applicable to the fine analysis of folding mechanisms in fast folding proteins. (Figure Presented).

U2 - 10.1021/jacs.5b02324

DO - 10.1021/jacs.5b02324

M3 - Journal article

C2 - 25924808

AN - SCOPUS:84930201934

SN - 0002-7863

VL - 137

SP - 6506

EP - 6516

JO - Journal of the American Chemical Society

JF - Journal of the American Chemical Society

IS - 20

ER -