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Guide for determination of protein structural ensembles by combining cryo-EM data with metadynamics.

Published version
Peer-reviewed

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Authors

Brotzakis, Z Faidon  ORCID logo  https://orcid.org/0000-0001-7024-1430

Abstract

Metadynamics electron microscopy metaInference (MEMMI) is an integrative structural biology method that enables a rapid and accurate characterization of protein structural dynamics at the atomic level and the error in the cryo-EM experimental data, even in cases where conformations are separated by high energy barriers. It achieves this by incorporating (a) cryo-electron microscopy electron density maps with (b) metadynamic-enhanced-sampling molecular dynamics. Here, I showcase the setup and analysis protocol of MEMMI, used to discover the atomistic structural ensemble and error in the cryo-EM electron density map of the fuzzy coat of IAPP, a fibril implicated in type II diabetes.

Description

Funder: Federation of European Biochemical Societies; Id: http://dx.doi.org/10.13039/100012623


Funder: Bodossaki Foundation; Id: http://dx.doi.org/10.13039/501100002752

Keywords

Bayesian inference, cryo-EM, metadynamics, molecular dynamics, protein dynamics, structural biology, Humans, Cryoelectron Microscopy, Diabetes Mellitus, Type 2, Proteins, Molecular Dynamics Simulation, Molecular Conformation

Journal Title

FEBS Open Bio

Conference Name

Journal ISSN

2211-5463
2211-5463

Volume Title

Publisher

Wiley