# FFF: Fragments-Guided Flexible Fitting for Building Complete Protein Structures

arXiv: https://arxiv.org/abs/2308.03654 · HTML: https://mlsanity.com/paper/2308.03654/

## Key facts

- No citing papers in the map yet (data through 14 Oct 2026).
- Builds on 5 of its 29 references that are in the map.
- First posted on arXiv 7 Aug 2023.

## Builds on (most cited first, 5 of 5)

- [U-Net: Convolutional Networks for Biomedical Image Segmentation](https://mlsanity.com/paper/1505.04597/) (2015)
- [Faster R-CNN: Towards Real-Time Object Detection with Region Proposal Networks](https://mlsanity.com/paper/1506.01497/) (2015)
- [V-Net: Fully Convolutional Neural Networks for Volumetric Medical Image Segmentation](https://mlsanity.com/paper/1606.04797/) (2016)
- [Focal Loss for Dense Object Detection](https://mlsanity.com/paper/1708.02002/) (2017)
- [A^2-Net: Molecular Structure Estimation from Cryo-EM Density Volumes](https://mlsanity.com/paper/1901.00785/) (2019)

## Abstract (arXiv)

Cryo-electron microscopy (cryo-EM) is a technique for reconstructing the 3-dimensional (3D) structure of biomolecules (especially large protein complexes and molecular assemblies). As the resolution increases to the near-atomic scale, building protein structures de novo from cryo-EM maps becomes possible. Recently, recognition-based de novo building methods have shown the potential to streamline this process. However, it cannot build a complete structure due to the low signal-to-noise ratio (SNR) problem. At the same time, AlphaFold has led to a great breakthrough in predicting protein structures. This has inspired us to combine fragment recognition and structure prediction methods to build a complete structure. In this paper, we propose a new method named FFF that bridges protein structure prediction and protein structure recognition with flexible fitting. First, a multi-level recognition network is used to capture various structural features from the input 3D cryo-EM map. Next, protein structural fragments are generated using pseudo peptide vectors and a protein sequence alignment method based on these extracted features. Finally, a complete structural model is constructed using the predicted protein fragments via flexible fitting. Based on our benchmark tests, FFF outperforms the baseline methods for building complete protein structures.