z-logo
Premium
G‐Quadruplex Recognition by DARPIns through Epitope/Paratope Analogy **
Author(s) -
Miclot Tom,
Big Emmanuelle,
Terenzi Alessio,
Grandemange Stéphanie,
Barone Giampaolo,
Monari Antonio
Publication year - 2022
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.202201824
Subject(s) - paratope , computational biology , complementarity (molecular biology) , epitope , circular dichroism , molecular recognition , biology , g quadruplex , genetics , biophysics , physics , dna , biochemistry , molecule , quantum mechanics , antigen
We investigated the mechanisms leading to the specific recognition of Guanine Guadruplex (G4) by DARPins peptides, which can lead to the design of G4 s specific sensors. To this end we carried out all‐atom molecular dynamic simulations to unravel the interactions between specific nucleic acids, including human‐telomeric (h‐telo), Bcl‐2, and c‐Myc , with different peptides, forming a DARPin/G4 complex. By comparing the sequences of DARPin with that of a peptide known for its high affinity for c‐Myc , we show that the recognition cannot be ascribed to sequence similarity but, instead, depends on the complementarity between the three‐dimensional arrangement of the molecular fragments involved: the α‐helix/loops domain of DARPin and the G4 backbone. Our results reveal that DARPins tertiary structure presents a charged hollow region in which G4 can be hosted, thus the more complementary the structural shapes, the more stable the interaction.

This content is not available in your region!

Continue researching here.

Having issues? You can contact us here