| Description |
Proteins that fail to adopt thermodynamically tertiary structure under physiological conditions are termed Intrinsically Disordered Proteins (IDPs). Characterizing the structural states of IDPs has become an intense research focus due to the complex roles these proteins play in both normal and pathological physiology. We utilized atomistic, biomolecular simulations to characterize the conformational states of IDPs under macromolecular crowding stress. In order to test the hypothesis that IDPs become more globally compact upon crowding, 1 μs of aggregate atomistic molecular dynamics simulation and 5.25 μs of aggregate enhanced molecular dynamics simulation were performed on the non-crowded 107-residue λ N model IDP. A custom-built post-processing algorithm was used to investigate the impact of macromolecular crowding on the conformational states of the λ N protein. We found that λ N protein structure compacts with increasing levels of macromolecular crowding on average. Interestingly, we also report that intermediate levels of crowding stabilize λ N structures towards experimentally-observed global structural conformations. Understanding the conformations of normal-functioning IDPs under physiologically realistic conditions is useful to better establish a reference point for their possible implication in disease. |
