QMDec 17, 2024
Generative modeling of protein ensembles guided by crystallographic electron densitiesSai Advaith Maddipatla, Nadav Bojan Sellam, Sanketh Vedula et al.
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.