pLDDT-Predictor: High-speed Protein Screening Using Transformer and ESM2
This enables rapid, large-scale protein structure quality assessments for researchers in structural biology and bioinformatics, though it is incremental as it builds on existing ESM2 and Transformer methods.
The paper tackles the computational bottleneck of high-throughput protein screening by introducing pLDDT-Predictor, which achieves a 250,000x speedup over AlphaFold2 with a Pearson correlation of 0.7891 for predicting pLDDT scores and processes proteins in 0.007 seconds on average.
Recent advancements in protein structure prediction, particularly AlphaFold2, have revolutionized structural biology by achieving near-experimental accuracy ($\text{average RMSD} < 1.5\textÅ$). However, the computational demands of these models (approximately 30 minutes per protein on an RTX 4090) significantly limit their application in high-throughput protein screening. While large language models like ESM (Evolutionary Scale Modeling) have shown promise in extracting structural information directly from protein sequences, rapid assessment of protein structure quality for large-scale analyses remains a major challenge. We introduce pLDDT-Predictor, a high-speed protein screening tool that achieves a $250,000\times$ speedup compared to AlphaFold2 by leveraging pre-trained ESM2 protein embeddings and a Transformer architecture. Our model predicts AlphaFold2's pLDDT (predicted Local Distance Difference Test) scores with a Pearson correlation of 0.7891 and processes proteins in just 0.007 seconds on average. Using a comprehensive dataset of 1.5 million diverse protein sequences (ranging from 50 to 2048 amino acids), we demonstrate that pLDDT-Predictor accurately classifies high-confidence structures (pLDDT $>$ 70) with 91.2\% accuracy and achieves an MSE of 84.8142 compared to AlphaFold2's predictions. The source code and pre-trained models are freely available at https://github.com/jw-chae/pLDDT_Predictor, enabling the research community to perform rapid, large-scale protein structure quality assessments.