Exploring Aromatic Cage Flexibility Using Cosolvent Molecular Dynamics SimulationsâAn In-Silico Case Study of Tudor Domains.
J Chem Inf Model
; 64(11): 4553-4569, 2024 Jun 10.
Article
em En
| MEDLINE
| ID: mdl-38771194
ABSTRACT
Cosolvent molecular dynamics (MD) simulations have proven to be powerful in silico tools to predict hotspots for binding regions on protein surfaces. In the current study, the method was adapted and applied to two Tudor domain-containing proteins, namely Spindlin1 (SPIN1) and survival motor neuron protein (SMN). Tudor domains are characterized by so-called aromatic cages that recognize methylated lysine residues of protein targets. In the study, the conformational transitions from closed to open aromatic cage conformations were investigated by performing MD simulations with cosolvents using six different probe molecules. It is shown that a trajectory clustering approach in combination with volume and atomic distance tracking allows a reasonable discrimination between open and closed aromatic cage conformations and the docking of inhibitors yields very good reproducibility with crystal structures. Cosolvent MDs are suitable to capture the flexibility of aromatic cages and thus represent a promising tool for the optimization of inhibitors.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Solventes
/
Simulação de Dinâmica Molecular
Idioma:
En
Revista:
J Chem Inf Model
Assunto da revista:
INFORMATICA MEDICA
/
QUIMICA
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Alemanha