Learning Scalar Fields for Molecular Docking with Fast Fourier Transforms

Published: 28 Oct 2023, Last Modified: 24 Nov 2023NeurIPS2023-AI4Science PosterEveryoneRevisionsBibTeX
Keywords: drug discovery, molecular docking, protein structure, structural biology
Abstract: Molecular docking is critical to structure-based virtual screening, yet the throughput of such workflows is limited by the expensive optimization of scoring functions involved in most docking algorithms. We explore how machine learning can accelerate this process by learning a scoring function with a functional form that allows for more rapid optimization. Specifically, we define the scoring function to be the cross-correlation of multi-channel ligand and protein scalar fields parameterized by equivariant graph neural networks, enabling rapid optimization over rigid-body degrees of freedom with fast Fourier transforms. Moreover, the runtime of our approach can be amortized at several levels of abstraction, and is particularly favorable for virtual screening settings with a common binding pocket. We benchmark our scoring functions on two simplified docking-related tasks: decoy pose scoring and rigid conformer docking. Our method attains similar but faster performance on crystal structures compared to the Vina and Gnina scoring functions, and is more robust on computationally predicted structures.
Submission Track: Original Research
Submission Number: 59