Single-structure and ensemble refinement with cryo-EM maps and EMMIVox

Aims

The aim of this tutorial is to learn how to use PLUMED to perform single-structure and ensemble refinement using cryo-EM maps and EMMIVox. This lesson was given as part of the PLUMED masterclass series in 2022. It includes:

• A video that explain the theory covered and a second video which shows you how the exercises should be completed.
• Two tutorials that you should try to complete yourself.

Overview of the theory

The EMMIVox approach is described in the following publication:

S. E. Hoff, F. E. Thomasen, K. Lindorff-Larsen, M. Bonomi. Accurate model and ensemble refinement using cryo-electron microscopy maps and Bayesian inference. PLoS Comput. Biol. 20 (2024) e1012180. doi: 10.1371/journal.pcbi.1012180.

Installation instructions

Prerequisites and guide to install the software to perform EMMIVox simulations can be found here.

Resources

The data needed to complete the tutorials can be found here. You can clone this repository locally on your machine using the following command:

git clone https://github.com/maxbonomi/EMMIVox-Plumed-Tutorials.git  

This repository contains the following 2 directories:

• scripts: python scripts used for preprocessing and analysis of EMMIVox simulations
• tutorials: complete tutorials for single-structure and ensemble refinement

The system under study is a Tau filament resolved at 1.9 Angstrom by the Scheres group (PDB 7P6A, EMD 13223). The system is composed by 5 identical chains, for a total of 8335 solute atoms. We will simulate the system using the CHARMM36m force field in explicit TIP3P water, for a total of 40958 atoms. The reference is:

Shi, Y., Zhang, W., Yang, Y. et al. Structure-based classification of tauopathies. Nature 598, 359–363 (2021)

Tutorial 1: Single-structure refinement with EMMIVox

The first tutorial to perform single-structure refinement with EMMIVox can be accessed here.

Tutorial 2: Ensemble refinement with EMMIVox

The second tutorial to perform ensemble refinement with EMMIVox can be accessed here.

Flowchart

The flow chart shown below indicates the order in which you should consult the resources. You can click on the nodes to access the various resources. Follow the thick black lines for the best results. The resources that are connected by dashed lines are supplementary resources that you may find useful when completing the exercise.

flowchart TB;
  A[PLUMED syntax] -.-> D[Tutorial 1];
  B[Installation] ==> D;
  C[Lecture I] ==> D;
  C -.-> G[Lecture notes];
  G -.-> D;
  D ==> E[Tutorial 2];
  E ==> F[Lecture II];
  click A "../../../21/001/data/NAVIGATION.html" "This lesson teaches you the basic features of the PLUMED input syntax with a particular focus on PBCs and selection tools"
  click B "install.html" "Installation instructions"
  click C "video1.html" "A lecture that was given on November 28th 2022 as part of the PLUMED masterclass series that introduces you to the exercises in this lesson"
  click D "01.html" "First tutorial to perform single-structure refinement with EMMIVox"
  click E "02.html" "Second tutorial to perform ensemble refinement with EMMIVox"
  click F "video2.html" "A lecture that was given on December 5th 2022 as part of the PLUMED masterclass series that goes through the solutions to the exercises in the lesson"
  click G "slides_theory.html" "Slides of the theoretical lecture"

Click here to open manual pages for actions discussed in this tutorial.