MOLECULAR DYNAMIC SIMULATIONS ON THE FOLDING AND CONFORMATIONAL INSIGHTS OF THE TRUNCATED PEPTIDES

Abstract

A total of 120 ns molecular dynamics simulations was used to study the folding and conformational aspects of six peptides with different lengths (Pep19–25, Pep15–25, Pep1–25, Pep15–39, Pep1–40, and Pep1–50) truncated from the αβ-tubulin dimer. These truncated peptides were found to undergo distinct structural transitions, with Pep1–25 and Pep1–50 folding into their respective stable conformations whereas on the contrary for the others. All the six truncated peptides are more or less compact than the corresponding segments in the αβ-tubulin dimer. The most striking contraction was observed in Pep1–25, which folds in a similar manner of β-hairpin. Pep1–50 has the least contraction and its folded conformation is the closest to that in the αβ-tubulin dimer. Moreover, the same conversions of β12–β23 from helices to hydrogen-bonded turns were witnessed in both Pep1–50 and the αβ-tubulin dimer. The structural instabilities of Pep19–25, Pep15–25, Pep15–39, and Pep1–40 were caused by the lack of long-distance interactions or/and the absence of key residues, with the details given in the discussions. The folding and conformational divergences of six truncated peptides were also observed in their active peptide segments ( Ap 15–25). Ap 15–25 in Pep1–50 achieves the best agreements with the αβ-tubulin dimer, implying that the local structure of Ap 15–25 in the αβ-tubulin dimer can be well reserved in Pep1–50 rather than in the other truncated peptides. The long-distance interactions, especially the key residues (e.g. β48-Arg), play a crucial role in the correct folding of Ap 15–25. The correct folding into the stable conformations is a prerequisite for the peptides to implement their catalytic actions, and therefore the present results are helpful to the future designs of active peptides.