论文标题
通过基于结构的深融合推断,改善了蛋白质 - 配体结合亲和力预测
Improved Protein-ligand Binding Affinity Prediction with Structure-Based Deep Fusion Inference
论文作者
论文摘要
预测准确的蛋白质 - 配体结合亲和力在药物发现中很重要,但即使使用基于计算昂贵的生物物理学的能量评分方法和最新的深度学习方法,也仍然是一个挑战。尽管基于深度卷积和图神经网络的方法最近取得了进步,但模型性能取决于输入数据表示,并且受到了不同的局限性。结合互补特征及其从单个模型中的推论以进行更好的预测是很自然的。我们提出了融合模型,以从两个神经网络模型的不同特征表示中受益,以改善结合亲和力预测。我们通过使用PDBBIND 2016数据集及其对接姿势复合物进行实验来证明所提出的方法的有效性。结果表明,与基于生物物理学的基于生物物理学的能量评分功能相比,与具有更高计算效率的个别神经网络模型相比,提出的方法可以改善总体预测。我们还讨论了提出的融合推断与几个示例复合物的好处。该软件可作为开源,网址为https://github.com/llnl/fast。
Predicting accurate protein-ligand binding affinity is important in drug discovery but remains a challenge even with computationally expensive biophysics-based energy scoring methods and state-of-the-art deep learning approaches. Despite the recent advances in the deep convolutional and graph neural network based approaches, the model performance depends on the input data representation and suffers from distinct limitations. It is natural to combine complementary features and their inference from the individual models for better predictions. We present fusion models to benefit from different feature representations of two neural network models to improve the binding affinity prediction. We demonstrate effectiveness of the proposed approach by performing experiments with the PDBBind 2016 dataset and its docking pose complexes. The results show that the proposed approach improves the overall prediction compared to the individual neural network models with greater computational efficiency than related biophysics based energy scoring functions. We also discuss the benefit of the proposed fusion inference with several example complexes. The software is made available as open source at https://github.com/llnl/fast.