Abstract
Proteins that lack tertiary stability under normal conditions, known as intrinsically disordered, exhibit a wide range of biological activities. Molecular descriptions for the biology of intrinsically disordered proteins (IDPs) consequently rely on disordered structural models, which in turn require experiments that assess the origins to structural features observed. For example, while hydrodynamic size is mostly insensitive to sequence composition in chemically denatured proteins, IDPs show strong sequence-specific effects in the hydrodynamic radius (Rh ) when measured under normal conditions. To investigate sequence-modulation of IDP Rh , disordered ensembles generated by a hard sphere collision model modified with a structure-based parameterization of the solution energetics were used to parse the contributions of net charge, main chain dihedral angle bias, and excluded volume on hydrodynamic size. Ensembles for polypeptides 10-35 residues in length were then used to establish power-law scaling relationships for comparison to experimental Rh from 26 IDPs. Results showed the expected outcomes of increased hydrodynamic size from increases in excluded volume and net charge, and compaction from chain-solvent interactions. Chain bias representing intrinsic preferences for α helix and polyproline II (PPII ), however, modulated Rh with intricate dependence on the simulated propensities. PPII propensities at levels expected in IDPs correlated with heightened Rh sensitivity to even weak α helix propensities, indicating bias for common (φ, ψ) are important determinants of hydrodynamic size. Moreover, data show that IDP Rh can be predicted from sequence with good accuracy from a small set of physicochemical properties, namely intrinsic conformational propensities and net charge. Proteins 2017; 85:296-311. © 2016 Wiley Periodicals, Inc.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.