Understanding the Reversible Binding of a Multichain Protein-Protein Complex through Free-Energy Calculations.
J Phys Chem B
; 128(15): 3598-3604, 2024 Apr 18.
Article
en En
| MEDLINE
| ID: mdl-38574232
ABSTRACT
We demonstrate that the binding affinity of a multichain protein-protein complex, insulin dimer, can be accurately predicted using a streamlined route of standard binding free-energy calculations. We find that chains A and C, which do not interact directly during binding, stabilize the insulin monomer structures and reduce the binding affinity of the two monomers, therefore enabling their reversible association. Notably, we confirm that although classical methods can estimate the binding affinity of the insulin dimer, conventional molecular dynamics, enhanced sampling algorithms, and classical geometrical routes of binding free-energy calculations may not fully capture certain aspects of the role played by the noninteracting chains in the binding dynamics. Therefore, this study not only elucidates the role of noninteracting chains in the reversible binding of the insulin dimer but also offers a methodological guide for investigating the reversible binding of multichain protein-protein complexes utilizing streamlined free-energy calculations.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Simulación de Dinámica Molecular
/
Insulina
Idioma:
En
Revista:
J Phys Chem B
Asunto de la revista:
QUIMICA
Año:
2024
Tipo del documento:
Article
País de afiliación:
China