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.