Intrinsically disordered proteins (IDPs) are a unique class of proteins without stable native structures. Like globular proteins, the structure and the dynamics of IDPs are also encoded in their amino acid sequences. IDPs usually contain a larger proportion of hydrophilic or charged amino acids than globular proteins. Interestingly, even with the same hydrophobicity and number of charged residues, the differences in sequence arrangement can lead to different structures of the peptides. In this work, to model such an effect, we conduct molecular simulations based on a series of peptides with randomly composed of charged residues (including glutamic acids and lysines) and isoleucine. In the simulation, we use the ABSINTH (self-Assembly of Biomolecules Studied by an Implicit, Novel, and Tunable Hamiltonian) implicit solvation model and employ the all-atom Markov Chain Monte Carlo method with replica-exchange sampling. Our simulations clearly show a transition between the extended conformations to compact structures for each peptide. The corresponding transition temperature is found to be dependent on the portion of the hydrophobic and charged residues. When the mean hydrophobicity is larger than a certain threshold, the transition temperature is higher than the room temperature, and vice versa. Such a result has outlined the borderline between intrinsically disordered proteins and the folded proteins. It is also consistent with previous analysis based on bioinformatics techniques. Furthermore, the contributions of different kinds of interactions to the structural variation of peptides are analyzed based on the contact statistics and the charge-pattern dependence of the gyration radii of the peptides. Our simulation results imply that the hydrophobicity of the sequence dominates the order-disorder transitions of IDPs, while the charge distribution can also affect such transitions. Based on these results, we achieve a comprehensive understanding of the sequence-structure relation of the natural proteins and the underlying physics. Our results may broaden our perspective of the sequence-structure relation of protein systems and shed light on the design of both ordered and disordered proteins.

Key words: intrinsically disordered protein, conformation, sequence, hydrophobicity, Monte Carlo simulations