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

TL;DR

This paper introduces FFF, a novel method combining fragment recognition and structure prediction to build complete protein structures from cryo-EM maps, overcoming low SNR issues and outperforming baseline methods.

Contribution

The paper presents FFF, a new approach that integrates recognition-based fragment generation with flexible fitting, enhancing complete protein structure modeling from cryo-EM data.

Findings

FFF outperforms baseline methods in benchmark tests.

The method effectively captures structural features from cryo-EM maps.

It successfully constructs complete protein models using predicted fragments.

Abstract

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.