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The PentaFOLD 3.0 Algorithm for the Selection of Stable Elements of Secondary Structure to be Included in Vaccine Peptides

[ Vol. 28 , Issue. 5 ]

Author(s):

Vladislav V. Khrustalev*   Pages 573 - 588 ( 16 )

Abstract:


Aims: The aim of this study was to create a new version of the PentaFOLD algorithm and to test its performance experimentally in several proteins and peptides.

Background: Synthetic vaccines can cause production of neutralizing antibodies only in case if short peptides form the same secondary structure as fragments of full-length proteins. The Penta- FOLD 3.0 algorithm was designed to check stability of alpha helices, beta strands, and random coils using several propensity scales obtained during analysis of 1730 3D structures of proteins.

Objective: The algorithm has been tested in the three peptides known to keep the secondary structure of the corresponding fragments of full-length proteins: the NY25 peptide from the Influenza H1N1 hemagglutinin, the SF23 peptide from the diphtheria toxin, the NQ21 peptide from the HIV1 gp120; as well as in the CC36 peptide from the human major prion protein.

Methods: Affine chromatography for antibodies against peptides accompanied by circular dichroism and fluorescence spectroscopy were used to check the predictions of the algorithm.

Result: Immunological experiments showed that all abovementioned peptides are more or less immunogenic in rabbits. The fact that antibodies against the NY25, the SF23, and the NQ21 form stable complexes with corresponding full-length proteins has been confirmed by affine chromatography. The surface of SARS CoV-2 spike receptor-binding domain interacting with hACE2 has been shown to be unstable according to the results of the PentaFOLD 3.0.

Conclusion: The PentaFOLD 3.0 algorithm (http://chemres.bsmu.by/PentaFOLD30.htm) can be used with the aim to design vaccine peptides with stable secondary structure elements.

Keywords:

Synthetic vaccine, secondary structure of proteins, hemagglutinin, diphtheria toxin, HIV1 gp120, human prion protein, SARS CoV-2.

Affiliation:

Department of General Chemistry, Belarusian State Medical University, Minsk



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