Conformational behaviour of Temporin A and Temporin L in aqueous solution: a computational/experimental study

Molecular dynamics (MD) simulations and circular dichroism (CD) experiments were carried out on aqueous temporin A and L, two short peptides belonging to an interesting class of natural substances known to be active mainly against Gram-positive/negative bacteria and,fungi. Experimental results indicate the higher propensity of temporin L, with respect to temporin A, in forming alpha-helical structures. These results were revisited by long-timescale MD simulations, in which their alpha-helical propensity was investigated in the absence of trifluoroethanol. Results clearly show the higher stability of alpha-helix conformations in temporin L; moreover, an interestingly strong mechanical analogy emerges since both temporins show the same residue interval (from 7 to 10) as the most energetically accessible for alpha-helix formation. Such studies provide some intriguing structural and mechanical evidence that may help in better understanding and rationalizing the conformational behaviour of temporins in water solution and, ultimately, the inner principles of their microbial targets selectivity and mechanism of action at the level of cell membranes.