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:
A brief introduction to the theory and advantage in using AlphaFold-Metainference.
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.
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
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).
Dr. Faidon Brotzakis ([email protected], [email protected])
Hussein Murtada ([email protected])
Prof. Michele Vendruscolo ([email protected])