Completion of partial structures using Patterson maps with the CrysFormer machine learning model

TL;DR

This paper presents a novel hybrid deep learning approach combining crystallographic data and predicted structures to improve protein structure determination, specifically in completing partial structures and refining electron density maps.

Contribution

It introduces a hybrid 3D vision transformer and convolutional network that directly incorporates experimental crystallographic data with predicted structures for enhanced structure completion.

Findings

Effective at completing partial structures from limited data

Improves phases of structure factors in crystallography

Enhances agreement between electron density maps and atomic models

Abstract

Protein structure determination has long been one of the primary challenges of structural biology, to which deep machine learning (ML)-based approaches have increasingly been applied. However, these ML models generally do not incorporate the experimental measurements directly, such as X-ray crystallographic diffraction data. To this end, we explore an approach that more tightly couples these traditional crystallographic and recent ML-based methods, by training a hybrid 3-d vision transformer and convolutional network on inputs from both domains. We make use of two distinct input constructs / Patterson maps, which are directly obtainable from crystallographic data, and ``partial structure'' template maps derived from predicted structures deposited in the AlphaFold Protein Structure Database with subsequently omitted residues. With these, we predict electron density maps that are then post-processed into atomic models through standard crystallographic refinement processes. Introducing an initial dataset of small protein fragments taken from Protein Data Bank entries and placing them in hypothetical crystal settings, we demonstrate that our method is effective at both improving the phases of the crystallographic structure factors and completing the regions missing from partial structure templates, as well as improving the agreement of the electron density maps with the ground truth atomic structures.