Generative modeling of protein ensembles guided by crystallographic electron densities

• URL: http://arxiv.org/abs/2412.13223v1
• Date: Tue, 17 Dec 2024 00:31:59 GMT
• Title: Generative modeling of protein ensembles guided by crystallographic electron densities
• Authors: Sai Advaith Maddipatla, Nadav Bojan Sellam, Sanketh Vedula, Ailie Marx, Alex Bronstein,
• Abstract summary: We propose a non-i.i.d. ensemble guidance approach to solve this problem. We demonstrate that it accurately recovers complicated multi-modal alternate protein backbone conformations observed in certain single crystal measurements.
• Score: 1.026104527280739
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• Abstract: Proteins are dynamic, adopting ensembles of conformations. The nature of this conformational heterogenity is imprinted in the raw electron density measurements obtained from X-ray crystallography experiments. Fitting an ensemble of protein structures to these measurements is a challenging, ill-posed inverse problem. We propose a non-i.i.d. ensemble guidance approach to solve this problem using existing protein structure generative models and demonstrate that it accurately recovers complicated multi-modal alternate protein backbone conformations observed in certain single crystal measurements.

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