Unbiased MD simulations identify lipid binding sites in lipid transfer proteins.
J Cell Biol
; 223(11)2024 Nov 04.
Article
em En
| MEDLINE
| ID: mdl-39105757
ABSTRACT
The characterization of lipid binding to lipid transfer proteins (LTPs) is fundamental to understand their molecular mechanism. However, several structures of LTPs, and notably those proposed to act as bridges between membranes, do not provide the precise location of their endogenous lipid ligands. To address this limitation, computational approaches are a powerful alternative methodology, but they are often limited by the high flexibility of lipid substrates. Here, we develop a protocol based on unbiased coarse-grain molecular dynamics simulations in which lipids placed away from the protein can spontaneously bind to LTPs. This approach accurately determines binding pockets in LTPs and provides a working hypothesis for the lipid entry pathway. We apply this approach to characterize lipid binding to bridge LTPs of the Vps13-Atg2 family, for which the lipid localization inside the protein is currently unknown. Overall, our work paves the way to determine binding pockets and entry pathways for several LTPs in an inexpensive, fast, and accurate manner.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Ligação Proteica
/
Proteínas de Transporte
/
Simulação de Dinâmica Molecular
Idioma:
En
Revista:
J Cell Biol
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Suíça
País de publicação:
Estados Unidos