DLAB: deep learning methods for structure-based virtual screening of antibodies

Bioinformatics. 2022 Jan 3;38(2):377-383. doi: 10.1093/bioinformatics/btab660.

Abstract

Motivation: Antibodies are one of the most important classes of pharmaceuticals, with over 80 approved molecules currently in use against a wide variety of diseases. The drug discovery process for antibody therapeutic candidates however is time- and cost-intensive and heavily reliant on in vivo and in vitro high throughput screens. Here, we introduce a framework for structure-based deep learning for antibodies (DLAB) which can virtually screen putative binding antibodies against antigen targets of interest. DLAB is built to be able to predict antibody-antigen binding for antigens with no known antibody binders.

Results: We demonstrate that DLAB can be used both to improve antibody-antigen docking and structure-based virtual screening of antibody drug candidates. DLAB enables improved pose ranking for antibody docking experiments as well as selection of antibody-antigen pairings for which accurate poses are generated and correctly ranked. We also show that DLAB can identify binding antibodies against specific antigens in a case study. Our results demonstrate the promise of deep learning methods for structure-based virtual screening of antibodies.

Availability and implementation: The DLAB source code and pre-trained models are available at https://github.com/oxpig/dlab-public.

Supplementary information: Supplementary data are available at Bioinformatics online.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies / chemistry
  • Antigens
  • Deep Learning*
  • Software

Substances

  • Antibodies
  • Antigens