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Published in

arXiv, 2022

DOI: 10.48550/arxiv.2206.12667

American Institute of Physics, The Journal of Chemical Physics, 17(158), 2023

DOI: 10.1063/5.0141474

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Learning to evolve structural ensembles of unfolded and disordered proteins using experimental solution data

This paper was not found in any repository, but could be made available legally by the author.
This paper was not found in any repository, but could be made available legally by the author.

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Abstract

The structural characterization of proteins with a disorder requires a computational approach backed by experiments to model their diverse and dynamic structural ensembles. The selection of conformational ensembles consistent with solution experiments of disordered proteins highly depends on the initial pool of conformers, with currently available tools limited by conformational sampling. We have developed a Generative Recurrent Neural Network (GRNN) that uses supervised learning to bias the probability distributions of torsions to take advantage of experimental data types such as nuclear magnetic resonance J-couplings, nuclear Overhauser effects, and paramagnetic resonance enhancements. We show that updating the generative model parameters according to the reward feedback on the basis of the agreement between experimental data and probabilistic selection of torsions from learned distributions provides an alternative to existing approaches that simply reweight conformers of a static structural pool for disordered proteins. Instead, the biased GRNN, DynamICE, learns to physically change the conformations of the underlying pool of the disordered protein to those that better agree with experiments.