Ligand-Induced Biased Activation of GPCRs: Recent Advances and New Directions from In Silico Approaches

Molecules, Год журнала: 2025, Номер 30(5), С. 1047 - 1047

Опубликована: Фев. 25, 2025

G-protein coupled receptors (GPCRs) are the largest family of membrane proteins engaged in transducing signals from extracellular environment into cell. GPCR-biased signaling occurs when two different ligands, sharing same binding site, induce distinct pathways. This selective offers significant potential for design safer and more effective drugs. Although its molecular mechanism remains elusive, big efforts made to try explain this using a wide range methods. Recent advances computational techniques AI technology have introduced variety simulations machine learning tools that facilitate modeling GPCR signal transmission analysis ligand-induced biased signaling. In review, we present current state silico approaches elucidate structural includes dynamics capture main interactions causing bias. We also highlight major contributions impacts transmembrane domains, loops, mutations mediating Moreover, discuss impact models on bias prediction diffusion-based generative ligands. Ultimately, review addresses future directions studying problem through approaches.

Язык: Английский

Molecular dynamics and machine learning stratify motion-dependent activity profiles of S-layer destabilizing nanobodies

PNAS Nexus, Год журнала: 2024, Номер 3(12)

Опубликована: Ноя. 26, 2024

Nanobody (Nb)-induced disassembly of surface array protein (Sap) S-layers, a two-dimensional paracrystalline lattice from

Язык: Английский