用Transformer和ESM2快速预测蛋白质结构质量,提速25万倍。
pLDDT-Predictor: High-speed Protein Screening Using Transformer and ESM2
- 基于预训练的ESM2嵌入与Transformer架构,实现高速结构质量评估。
- 平均0.007秒/蛋白,对pLDDT预测相关性达0.7891,准确率91.2%。
- 适合大规模蛋白筛选,支持高通量结构质量初筛,开源可用。
近年来,AlphaFold2等蛋白质结构预测模型已实现近实验精度(平均RMSD < 1.5Å),但其计算成本极高(单蛋白约需30分钟,使用RTX 4090)。尽管ESM等大语言模型能从序列中提取结构信息,但针对大规模分析的快速结构质量评估仍是挑战。本文提出pLDDT-Predictor,利用预训练的ESM2蛋白嵌入与Transformer架构,实现相比AlphaFold2高达25万倍的加速。该模型平均仅需0.007秒/蛋白,对AlphaFold2的pLDDT得分预测相关系数为0.7891,准确分类高置信度结构(pLDDT > 70)达91.2%,均方误差为84.8142。基于包含150万条多样蛋白序列(长度50–2048个氨基酸)的数据集验证了其有效性。代码与预训练模型已开源,支持研究社区进行快速、大规模的蛋白质结构质量评估。
原文摘要 · Abstract (English)
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.
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