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

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.

Keywords

• Bayesian inference
• cryo‐EM
• metadynamics
• molecular dynamics
• protein dynamics
• structural biology