G-Quadruplex Recognition by DARPIns through Epitope/Paratope Analogy.
Chemistry
; 28(57): e202201824, 2022 Oct 12.
Article
en En
| MEDLINE
| ID: mdl-35791808
ABSTRACT
We investigated the mechanisms leading to the specific recognition of Guanine Guadruplex (G4) by DARPins peptides, which can lead to the design of G4â
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.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Ácidos Nucleicos
/
G-Cuádruplex
Límite:
Humans
Idioma:
En
Año:
2022
Tipo del documento:
Article