Related Experiment Video
Updated: Jul 25, 2025

Protein WISDOM: A Workbench for In silico De novo Design of BioMolecules
Published on: July 25, 2013
Improvement of protein tertiary and quaternary structure predictions using the ReFOLD refinement method and the
Recep Adiyaman1, Nicholas S Edmunds1, Ahmet G Genc1
1School of Biological Sciences, University of Reading, Reading RG6 6EX, UK.
Motivation:
The accuracy gap between predicted and experimental structures has been significantly reduced following the development of AlphaFold2 (AF2). However, for many targets, AF2 models still have room for improvement. In previous CASP experiments, highly computationally intensive MD simulation-based methods have been widely used to improve the accuracy of single 3D models. Here, our ReFOLD pipeline was adapted to refine AF2 predictions while maintaining high model accuracy at a modest computational cost. Furthermore, the AF2 recycling process was utilized to improve 3D models by using them as custom template inputs for tertiary and quaternary structure predictions.
Results:
According to the Molprobity score, 94% of the generated 3D models by ReFOLD were improved. AF2 recycling showed an improvement rate of 87.5% (using MSAs) and 81.25% (using single sequences) for monomeric AF2 models and 100% (MSA) and 97.8% (single sequence) for monomeric non-AF2 models, as measured by the average change in lDDT. By the same measure, the recycling of multimeric models showed an improvement rate of as much as 80% for AF2-Multimer (AF2M) models and 94% for non-AF2M models.
Availability And Implementation:
Refinement using AlphaFold2-Multimer recycling is available as part of the MultiFOLD docker package (https://hub.docker.com/r/mcguffin/multifold). The ReFOLD server is available at https://www.reading.ac.uk/bioinf/ReFOLD/ and the modified scripts can be downloaded from https://www.reading.ac.uk/bioinf/downloads/.
Supplementary Information:
Supplementary data are available at Bioinformatics Advances online.
Related Concept Videos
Protein Folding
Protein Structure Is Critical to Its Biological Function
Proteins perform a wide range of biological functions such as catalyzing chemical reactions, providing...
Protein Folding Quality Check in the RER
Conservation of Protein Domains Over Different Proteins
A limited set of protein domains often duplicate and recombine during evolution. These domains can be organized in different combinations to...
Protein Organization
The primary structure of a protein is its amino acid sequence....
Molecular Chaperones and Protein Folding
The...
Amyloid Fibrils
Amyloid deposits were observed as early as 1639 in the liver and the spleen. In 1854, Rudolph Virchow performed iodine staining,...

