Prediction of interface between regions of varying degrees of order or disorderness in intrinsically disordered proteins from dihedral angles

Abstract

Intrinsically disordered proteins (IDPs) are proteins that do not form uniquely defined three-dimensional (3-D) structures. Experimental research on IDPs is difficult since they go against the traditional protein structure-function paradigm. Although there are several predictors of disorder based on amino acid sequences, but very limited based on the 3-D structures of proteins. Dihedral angles have a significant role in predicting protein structure because they establish a protein’s backbone, which, coupled with its side chain, establishes its overall shape. Here, we have carried out atomistic Molecular Dynamics (MD) simulations on four different proteins: one ordered protein (Monellin), two partially disordered proteins (p53-TAD and Amyloid beta (Aβ_1-42) peptide), and one completely disordered protein (Histatin 5). The MD simulation trajectories for the corresponding four proteins were used to conduct dihedral angle (ϕ and ѱ) analysis. Then, the average dihedral angles for each of the residues were calculated and plotted against the residue index. We noticed steep rises or falls in the average ϕ value at certain locations in the plot. These sudden shifts in the average ϕ value reflect the interface between regions of varying degrees of order or disorderness in intrinsically disordered proteins. Using this method, the probable conformer of a protein with a higher degree of disorder can be found among the ensembles of structures sampled during the MD simulations. The results of our study offer new understandings on precisely identifying regions of various degrees of disorder in intrinsically disordered proteins.

Communicated by Ramaswamy H. Sarma

Keywords:

• Dihedral angle
• intrinsically disordered proteins
• molecular dynamics simulations
• disordered regions
• unstructured proteins

Acknowledgments

The authors extend their deepest gratitude to Tezpur University and University Grants Commission, India, for the start-up grant and to Department of Molecular Biology and Biotechnology, Tezpur University for providing adequate computational facility.

Disclosure statement

The authors declare no competing financial interest.

Authors’ contributions

The manuscript was written through contributions of all authors. All authors have given approval to the final version of the manuscript.

Additional information

Funding

The author(s) reported there is no funding associated with the work featured in this article.