Publications

Topics:
  1. A. Maddipatla, N. Bojan Sellam, M. Bojan, S. Vedula, P. Schanda, A. Marx, A. M. Bronstein, Inverse problems with experiment-guided AlphaFold, arXiv:2502.09372, 2025 details

    Inverse problems with experiment-guided AlphaFold

    A. Maddipatla, N. Bojan Sellam, M. Bojan, S. Vedula, P. Schanda, A. Marx, A. M. Bronstein
    arXiv:2502.09372, 2025

    Proteins exist as a dynamic ensemble of multiple conformations, and these motions are often crucial for their functions. However, current structure prediction methods predominantly yield a single conformation, overlooking the conformational heterogeneity revealed by diverse experimental modalities. Here, we present a framework for building experiment-grounded protein structure generative models that infer conformational ensembles consistent with measured experimental data. The key idea is to treat state-of-the-art protein structure predictors (e.g., AlphaFold3) as sequence-conditioned structural priors, and cast ensemble modeling as posterior inference of protein structures given experimental measurements. Through extensive real-data experiments, we demonstrate the generality of our method to incorporate a variety of experimental measurements. In particular, our framework uncovers previously unmodeled conformational heterogeneity from crystallographic densities, and generates high-accuracy NMR ensembles orders of magnitude faster than the status quo. Notably, we demonstrate that our ensembles outperform AlphaFold3 and sometimes better fit experimental data than publicly deposited structures to the Protein Data Bank (PDB). We believe that this approach will unlock building predictive models that fully embrace experimentally observed conformational diversity.

    Y. Davidson, A. Philipp, S. Chakraborty, A. M. Bronstein, R. Gershoni-Poranne, How local is "local"? Deep learning reveals locality of the induced magnetic field of polycyclic aromatic hydrocarbons, chemrxiv 10.26434/chemrxiv-2025-pqmcc, 2025 details

    How local is "local"? Deep learning reveals locality of the induced magnetic field of polycyclic aromatic hydrocarbons

    Y. Davidson, A. Philipp, S. Chakraborty, A. M. Bronstein, R. Gershoni-Poranne
    chemrxiv 10.26434/chemrxiv-2025-pqmcc, 2025

    We investigate the locality of magnetic response in polycyclic aromatic molecules using a novel deep-learning approach. Our method employs graph neural networks (GNNs) with a graph-of-rings representation to predict Nucleus-Independent Chemical Shifts in the space around the molecule. We train a series of models, each time reducing the size of the largest molecules used in training. The accuracy of prediction remains high (MAE < 0.5 ppm), even when training the model only on molecules with up to 4 rings, thus providing strong evidence for the locality of magnetic response. To overcome the known problem of generalization of GNNs, we implement a k-hop expansion strategy and succeed in achieving accurate predictions for molecules with up to 15 rings (almost 4 times the size of the largest training example). Our findings have implications for understanding the magnetic response in complex molecules and demonstrate a promising approach to overcoming GNN scalability limitations. Furthermore, the trained models enable rapid characterization, without the need for more expensive DFT calculations.