NeuralPLexer3: Accurate Biomolecular Complex Structure Prediction with Flow Models
This work addresses challenges in structure-based drug design by providing more accurate and efficient predictions of biomolecular complexes, which is crucial for understanding diseases and developing therapeutics.
The authors tackled the problem of predicting biomolecular complex structures for drug discovery by developing NeuralPLexer3, a flow-based generative model that achieves state-of-the-art accuracy on key interaction types and improves efficiency in training and sampling compared to previous methods.
Structure determination is essential to a mechanistic understanding of diseases and the development of novel therapeutics. Machine-learning-based structure prediction methods have made significant advancements by computationally predicting protein and bioassembly structures from sequences and molecular topology alone. Despite substantial progress in the field, challenges remain to deliver structure prediction models to real-world drug discovery. Here, we present NeuralPLexer3 -- a physics-inspired flow-based generative model that achieves state-of-the-art prediction accuracy on key biomolecular interaction types and improves training and sampling efficiency compared to its predecessors and alternative methodologies. Examined through newly developed benchmarking strategies, NeuralPLexer3 excels in vital areas that are crucial to structure-based drug design, such as physical validity and ligand-induced conformational changes.