Dear Vito Kontrimas ,

Interesting question. One could argue that it in most cases will have no influence (since overall charge, hydrophobicity, hydrophobic moment etc. are the same).

However it has been examined and at least for the example investigated it had quite some consequences:

Ambroggio, E. E., Caruso, B., Villarreal, M. A., Raussens, V., & Fidelio, G. D. (2016). Reversing the peptide sequence impacts on molecular surface behaviour. Colloids and Surfaces B: Biointerfaces, 139, 25-32.

You can ask one of the authors here on RG for a full text version of this paper:

Article Reversing the peptide sequence impacts on molecular surface behaviour

On the level of folding and in your case when you talk about a peptide the secondary structure there is some interesting literature that seems to suggest that reversal of a sequence causing reversal of the direction of the termini and peptide bonds can have an effect. See for example:

Atzori, A., Baker, A. E., Chiu, M., Bryce, R. A., & Bonnet, P. (2013). Effect of sequence and stereochemistry reversal on p53 peptide mimicry. PloS one, 8(7).

Lacroix, E., Viguera, A. R., & Serrano, L. (1998). Reading protein sequences backwards. Folding and Design, 3(2), 79-85.

Hope this helps.

Best regards.

There is always a relationship between chemical structure and biological function: change the structure, and you will change the function. So the question has to be whether the structure will be the same, or largely the same.

In general if the sequence is reversed, it would not fold "correctly", or rather in it would not fold in the same way as the original amino acid sequence. Consequently it would change the functionality.

Dear @Vito Kontrimas, the aminoacid residues have a chiral centres and reversing the sequence will definitely change the structure of the peptide and eventually will change its function as the biological effects are greatly affected by the chemical structure.

For instance, many of the non-functional mutated-enzymes have as small as one different/deleted residue.

Hope this helps.

I agree with the opinions above, and a standard control in peptide studies is a "shuffled" sequence. Using this approach in my own work on cell-penetrating peptides, I found that density of positively charged amino acids was more important than amino acid sequence. In many assays Arg worked better than Lys.

Absolutely the reversing peptide sequence can change their function, In the same way can modify others properties such as lateral conductivity (conductivity on the surface of water by using Langmuir monolayer) even when the hydrophobicity and the sequence length are the same.

A recently work concerning about that

Stitching together a nm thick peptide-based semiconductor sheet using UV light. Alvarez AB, Pino M, Petersen SB, Fidelio GD. Colloids SurfB Biointerfaces. 2021 Jul;203:111734. doi: 10.1016/j.colsurfb.2021.111734.

Best Regards