In:
Chemistry – A European Journal, Wiley, Vol. 28, No. 57 ( 2022-10-12)
Abstract:
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.
Type of Medium:
Online Resource
ISSN:
0947-6539
,
1521-3765
DOI:
10.1002/chem.202201824
Language:
English
Publisher:
Wiley
Publication Date:
2022
detail.hit.zdb_id:
1478547-X
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