AlphaFold-Metainference tutorial

A tutorial to setup and run AlphaFold-Metainference simulations. The original work which explains the theory for AlphaFold-Metainference (AF-MI) can be found here.

The tutorial comprises the following sections:

AlphaFold-Metainference theory

A brief introduction to the theory and advantage in using AlphaFold-Metainference.

Case study: TDP-43 WtoA monomer dynamics

We will present the case study for this tutorial, the DNA/RNA processing protein TDP-43 which undergoes both functional and pathogennic aggregation in amyotrophic lateral sclerosis (ALS) and other neurodegenerative conditions. To enable a rapid structural ensemble generation on a laptop/workstation, AF-MI is coupled to the CALVADOS-2 coarse-grained forcefield.

Input files preparation

We will discuss all the preliminary steps to set up AF-MI, from generating the AF2 distance-map restraints data, to preparing PLUMED inputes, and running energy minimization and production runs

Structural ensemble generation and post-processing analysis

Finally, we will discuss how to generate the unbiased structural ensemble of TDP-43, estimate free energy surfaces along collective variables (CVs) and predict ensemble averaged properties such as secondary structureand RMSF.

NB: This tutorial assumes that you know metadynamics theory and practice in PLUMED (if not, a good start can be the PLUMED tutorial about it).

This tutorial has been contributed by

Dr. Faidon Brotzakis (fb516@cam.ac.uk, brotzakis@fleming.gr)

Hussein Murtada (mhm42@cam.ac.uk)

Prof. Michele Vendruscolo (mv245@cam.ac.uk)