Modelling IDPs

There are sufficiently accurate energy functions or force fields available to date for simulating the atomistically detailed structure of an IDP. But, the large computational time required to generate statistically significant conformations to compute the structural properties is a major limitation of the atomistic model. To overcome the limitation of the atomistic model, we used coarse-grained models for IDPs in which each amino acid residue of the protein is modeled by two interacting sites accounting for backbone and sidechain atoms of a residue. A quantitative agreement between simulated and experimental SAXS profiles for IDPs indicates our model can capture the experimental properties correctly. Structural characterization of IDPs reveals the polypeptide chains act as self avoiding walk (SAW) polymer present in good solvent. But unlike a homopolymer, there is significant heterogeneity in the frequency of contacts formed between two residues.

Normalized Kratky plot from experiments and simulations for (A) Sic1 (red) and Prothymosin (blue), (B) Nucleoporin (green), ERMTADn (violet) and IN (magenta). Experimental data is not available for IN. Light shaded dot and deep solid line are for corresponding experimental and simulated results, respectively. (C) Average radius of gyration of the IDPs from simulation are plotted against the experimentally measured values. The Pearson correlation coefficient for radius of gyration between experiment and simulation is ~0.93.

(A) Inter-residue distance is plotted as a function of separation between residues i and j on a log-log scale for prothymosin, sic1, IN, ERMTADn, and nucleoporin in blue pentagons, red diamonds, green triangles, magenta circles, and yellow rhombus, respectively. The dotted line in black corresponds to a polymer exhibiting SAW. (B) Structure factor for all the five IDPs is plotted as a function of scaled wave vector, where N is the number of residues in the IDP. The dotted line in black corresponds to a polymer behaving as a SAW. (C) Probability distribution of rescaled end-to-end distance distribution, P(X) are plotted for all the five IDPs. The universal P(X) for SAW is plotted in black dashed line.