Backbone reversal in a protein creates a retroprotein, when the last amino acid is placed first, the second-last amino acid is placed second,…and so on….such that the retroprotein has exactly the same sequence as the original protein, except that the direction in which the polypeptide backbone runs through the protein is exactly the opposite of what it was in the first place. In this paper, I argue – using logic and computation to support my arguments – that, in particular, for beta sheet-based proteins, it should be possible for a retroprotein to fold into a topological mirror-image of the original protein from which its sequence is derived. In other words, I propose that the retroprotein with its sequence derived from a beta sheet-based globular protein could fold into a mirror-image structure in which the scheme of sidechain packing would be mirrored, but there would be no atom-for-atom mirror imaging of the kind that would be obtained through inversion of the chirality of amino acids (D- to L-) while maintaining the same backbone direction. I also argued that performing the two transformations together, i.e., retro and inverso transformations, would be expected to result in the sidechain-packing scheme returning to that of the original protein; however, in the backbone, wherever there was a C=O group originally, there would now be an N-H group. Therefore, a retro transformation would achieve a topological mirror-imaging. An inverso transformation would achieve an atom-for-atom mirror imaging. And finally, a retro-inverso transformation would result in a likeness of the original protein, with C=O and N-H groups substituted for each other in the backbone, since it would constitute a mirror-imaging transformation followed by a mirror-imaging transformation, resulting in the return of all amino acid sidechains to their original positions in space.
This was my first paper as single author and corresponding author. I am indebted to my graduate advisor, Prof. D. Balasubramanian, with whom I was working on lens crystallins in the lab for my Ph.D, at that time, for generously allowing me to work on the side on some of my ideas and publish them independently.

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