GLDM: hit molecule generation with constrained graph latent diffusion model.
Brief Bioinform
; 25(3)2024 Mar 27.
Article
en En
| MEDLINE
| ID: mdl-38581415
ABSTRACT
Discovering hit molecules with desired biological activity in a directed manner is a promising but profound task in computer-aided drug discovery. Inspired by recent generative AI approaches, particularly Diffusion Models (DM), we propose Graph Latent Diffusion Model (GLDM)-a latent DM that preserves both the effectiveness of autoencoders of compressing complex chemical data and the DM's capabilities of generating novel molecules. Specifically, we first develop an autoencoder to encode the molecular data into low-dimensional latent representations and then train the DM on the latent space to generate molecules inducing targeted biological activity defined by gene expression profiles. Manipulating DM in the latent space rather than the input space avoids complicated operations to map molecule decomposition and reconstruction to diffusion processes, and thus improves training efficiency. Experiments show that GLDM not only achieves outstanding performances on molecular generation benchmarks, but also generates samples with optimal chemical properties and potentials to induce desired biological activity.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Benchmarking
/
Descubrimiento de Drogas
Idioma:
En
Revista:
Brief Bioinform
Asunto de la revista:
BIOLOGIA
/
INFORMATICA MEDICA
Año:
2024
Tipo del documento:
Article
País de afiliación:
Singapur