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Efficient Generation of Conformer Ensembles Using Internal Coordinates and a Generative Directional Graph Convolution Neural Network.
Raush, Eugene; Abagyan, Ruben; Totrov, Maxim.
Afiliación
  • Raush E; Molsoft L.L.C., 11199 Sorrento Valley Road, S209, San Diego, California 92121, United States.
  • Abagyan R; Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, California 92093, United States.
  • Totrov M; Molsoft L.L.C., 11199 Sorrento Valley Road, S209, San Diego, California 92121, United States.
J Chem Theory Comput ; 20(9): 4054-4063, 2024 May 14.
Article en En | MEDLINE | ID: mdl-38669307
ABSTRACT
We present a neural-network-based high-throughput molecular conformer-generation algorithm. A chemical graph-convolutional network is trained to predict low-energy conformers in internal coordinate representation (bond lengths, bond, and torsion angles), starting from two-dimensional (2D) chemical topology. Generative neural network (NN) architecture performs denoising from torsion space, producing conformer ensembles with populations that are well correlated with torsion energy profiles. Short force-field-based energy minimization is applied to refine final conformers. All computation-intensive stages of the algorithm are GPU-optimized. The procedure (termed GINGER) is benchmarked on a commonly used test set of bioactive three-dimensional (3D) conformers from the PDB. We demonstrate highly competitive results in conformer recovery and throughput rates suitable for giga-scale compound library processing. A web server that allows interactive conformer ensemble generation by GINGER and their viewing is made freely available at https//www.molsoft.com/gingerdemo.html.

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: J Chem Theory Comput Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: J Chem Theory Comput Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos