The accurate screening of candidate drug ligands against target proteins
through computational approaches is of prime interest to drug development
efforts, as filtering potential candidates would save time and expenses for
finding drugs. Such virtual screening depends in part on methods to predict the
binding affinity between ligands and proteins. Given many computational models
for binding affinity prediction with varying results across targets, we herein
develop a meta-modeling framework by integrating published empirical
structure-based docking and sequence-based deep learning models. In building
this framework, we evaluate many combinations of individual models, training
databases, and linear and nonlinear meta-modeling approaches. We show that many
of our meta-models significantly improve affinity predictions over individual
base models. Our best meta-models achieve comparable performance to
state-of-the-art exclusively structure-based deep learning tools. Overall, we
demonstrate that diverse modeling approaches can be ensembled together to gain
substantial improvement in binding affinity prediction while allowing control
over input features such as physicochemical properties or molecular
descriptors.

通过整合发布的经验结构基于对接和序列基于深度学习模型，我们开发了一个元建模框架，多个元模型在结合输入特征多样性的情况下，显著提高了结合亲和力预测的准确性，从而节省了找药物的时间和费用。