DiffModeler is a computational tool using a diffusion model to automatically build full protein complex structure from cryo-EM maps at intermediate and low resolution.
Copyright (C) 2023 Xiao Wang, Han Zhu, Genki Terashi, Daisuke Kihara, and Purdue University.
License: GPL v3. (If you are interested in a different license, for example, for commercial use, please contact us.)
For technical problems or questions, please reach to Xiao Wang (wang3702@purdue.edu).
Citation:
Xiao Wang, Han Zhu, Genki Terashi & Daisuke Kihara. Protein Complex Structure Modeling with Diffusion Model and AlphaFold in cryo-EM maps.bioArxiv, 2023.
@article{wang2023DiffModeler,
title={Protein Complex Structure Modeling with Diffusion Model and AlphaFold in cryo-EM maps},
author={Xiao Wang, Han Zhu, Genki Terashi, and Daisuke Kihara},
journal={bioArxiv},
year={2023}
}
Cryogenic electron microscopy (cryo-EM) has been widely employed in experimental settings to determine multi-chain protein complexes, but modeling accuracy greatly diminishes when resolution decreases. At intermediate resolutions of 5-10 Å, even template-based structure fitting presents significant challenges. To tackle this issue, we introduce DiffModeler, a fully automated protein complex structure modeling method that leverages a diffusion model for backbone tracing and structure fitting with AlphaFold predicted single-chain structure. In extensive testing on cryo-EM maps at intermediate resolution, DiffModeler showcased remarkably accurate structure modeling, surpassing existing methods significantly. Notably, we successfully modeled a protein complex consisting of 47 chains, comprising 13,462 residues, with an impressive TM-Score of 0.9. We also further benchmarked DiffModeler for maps at low resolution of 10-20 Å and validated its generalizability with plausible performances.
Overall Protocol
Backbone tracing from cryo-EM maps at intermediate resolution via diffusion model.
Single-chain structure prediction by AlphaFold.
Single-chain structure fitting using VESPER.
Protein complex modeling by assembling algorithms.
