I-TASSER-MTD: a deep-learning-based platform for multi-domain protein structure and function prediction

Nat Protoc. 2022 Oct;17(10):2326-2353. doi: 10.1038/s41596-022-00728-0. Epub 2022 Aug 5.

Abstract

Most proteins in cells are composed of multiple folding units (or domains) to perform complex functions in a cooperative manner. Relative to the rapid progress in single-domain structure prediction, there are few effective tools available for multi-domain protein structure assembly, mainly due to the complexity of modeling multi-domain proteins, which involves higher degrees of freedom in domain-orientation space and various levels of continuous and discontinuous domain assembly and linker refinement. To meet the challenge and the high demand of the community, we developed I-TASSER-MTD to model the structures and functions of multi-domain proteins through a progressive protocol that combines sequence-based domain parsing, single-domain structure folding, inter-domain structure assembly and structure-based function annotation in a fully automated pipeline. Advanced deep-learning models have been incorporated into each of the steps to enhance both the domain modeling and inter-domain assembly accuracy. The protocol allows for the incorporation of experimental cross-linking data and cryo-electron microscopy density maps to guide the multi-domain structure assembly simulations. I-TASSER-MTD is built on I-TASSER but substantially extends its ability and accuracy in modeling large multi-domain protein structures and provides meaningful functional insights for the targets at both the domain- and full-chain levels from the amino acid sequence alone.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, N.I.H., Extramural

MeSH terms

  • Algorithms
  • Computational Biology* / methods
  • Cryoelectron Microscopy
  • Databases, Protein
  • Deep Learning*
  • Models, Molecular
  • Protein Conformation
  • Proteins / chemistry

Substances

  • Proteins