Free Energy Landscape (FEL) analysis
Folding funnel is a fundamental concept in the free energy landscape of
ordered proteins. It helps in understanding the different conformational
ensembles explored by the protein throughout the simulations and how
they fold into an ensemble having a global energy minimum. Each funnel
in the free energy landscape diagram represents a reaction path in the
folding process, and ideally, a protein folds into its native structure,
having the lowest energy, with a single narrow funnel, where the
intermediate structures are represented within the funnel at higher
energy levels [47, 48]. But the folding scenario in IDP is
different, as they do not have proper tertiary structure and tend to
fold once bound to a binding partner. This indicates that the free
energy landscape of IDPs is rugged and contains multiple funnels
[49-51]. But they can provide insights into the folding pattern and
minimum energy conformations occupied by the protein. A FEL diagram was
generated for each of the simulated systems, with Radius of gyration and
End to end distance as the two reaction coordinates using the gmx sham
module [52] and and 2D contour plots and 3D projections of the free
energy are plotted in figure 4 and supporting informationFigure S4 respectively.