Hierarchical, rotation-equivariant neural networks to select structural models of protein complexes
This work addresses a grand challenge in biochemistry for basic science and drug discovery by enabling more accurate protein complex structure prediction, though it is incremental as it builds on prior scoring functions.
The authors tackled the problem of selecting accurate structural models of protein complexes by introducing a machine learning method that learns directly from atomic coordinates without pre-defined features, resulting in substantial improvement in model identification when combined with existing scoring functions.
Predicting the structure of multi-protein complexes is a grand challenge in biochemistry, with major implications for basic science and drug discovery. Computational structure prediction methods generally leverage pre-defined structural features to distinguish accurate structural models from less accurate ones. This raises the question of whether it is possible to learn characteristics of accurate models directly from atomic coordinates of protein complexes, with no prior assumptions. Here we introduce a machine learning method that learns directly from the 3D positions of all atoms to identify accurate models of protein complexes, without using any pre-computed physics-inspired or statistical terms. Our neural network architecture combines multiple ingredients that together enable end-to-end learning from molecular structures containing tens of thousands of atoms: a point-based representation of atoms, equivariance with respect to rotation and translation, local convolutions, and hierarchical subsampling operations. When used in combination with previously developed scoring functions, our network substantially improves the identification of accurate structural models among a large set of possible models. Our network can also be used to predict the accuracy of a given structural model in absolute terms. The architecture we present is readily applicable to other tasks involving learning on 3D structures of large atomic systems.