A Coarse-Grained Model for Unfolded Proteins

Abstract

There is increasing evidence that natively-unfolded proteins play a key role in many important biological processes, including nucleocytoplasmic transport. In this work we propose an implicit solvent one-bead per amino-acid coarse-grained molecular dynamics model to study the characteristics of unfolded proteins. Experimentally-obtained Ramachandran plots for the coil regions of proteins are converted into distributions of pseudo-bond and pseudo-dihedral angles between neighboring alpha-carbons in the polypeptide chain. These are then used to derive bending and torsion potentials, which are residue- and sequence-specific. We show that the radius of gyration of denatured proteins can be well predicted by the developed potentials. Figure 1 shows the radius of gyration (Rg) as a function of the number of residues (N) for a range of denatured proteins. Both our simulation results and experimental data can be well fitted to a power-law relation with a similar exponent. The experimental data are slightly overestimated, which could be explained by the presence of hydrophobic clusters and residual structures for the used experimental conditions. In future work our model will be extended to include hydrophobic and electrostatic effects as well.