Estimating Protein Complex Model Accuracy Using Graph Transformers and Pairwise Similarity Graphs.

Abstract

Motivation: Estimation of protein complex structure accuracy is an essential step in protein complex structure prediction and is also important for users to select good structural models for various applications, such as protein function analysis and drug design. Despite the success of structure prediction methods such as AlphaFold2 and AlphaFold3, predicting the quality of predicted complex structures (structural models) and selecting top ones from large model pools remains challenging.

Results: We present GATE, a novel method that uses graph transformers on pairwise model similarity graphs to predict the quality (accuracy) of complex structural models. By integrating single-model and multi-model quality features, GATE captures both the characteristics of individual models and the geometric similarity between them to make robust predictions. On the dataset of the 15th Critical Assessment of Protein Structure Prediction (CASP15), GATE achieved the highest Pearson's correlation (0.748) and the lowest ranking loss (0.1191) compared to existing methods. In the blind CASP16 experiment, GATE was ranked 4th according to the overall sum of z-scores of multiple metrics based on both TM-score and Oligo-GDTTS scores. In terms of per-target average metrics based on TM-score, GATE achieved a Pearson's correlation of 0.7076 (1st place among all methods), a Spearman's correlation of 0.4514 (3rd place), a ranking loss of 0.1221 (3rd place), and an Area Under the Curve (AUC) score of 0.6680 (3rd place), highlighting its strong, balanced ability of estimating complex model accuracy and selecting good models.

Availability: The source code of GATE is freely available at https://github.com/BioinfoMachineLearning/GATE.