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, please visit PLUMED tutorial).

flowchart TB
  A[PLUMED syntax] -.-> D[Theory];
  B[Parallel Bias Metadynamics] -.->  D;
  C[Metainference] -.-> D;
  D --> E[Case study];
  E --> F[Jupyter/Colab]
  F --> G[Inputs]
  G --> F[Jupyter/Colab]
  F --> H[Post-processing]

  click A "../../../21/001/data/NAVIGATION.html" "This lesson teaches you the basic features of the PLUMED input syntax"
  click B "https://www.plumed.org/doc-v2.9/user-doc/html/_p_b_m_e_t_a_d.html" "This lesson teaches you how to perform and analyze Metadynamics simulations"
  click C "https://www.plumed.org/doc-v2.9/user-doc/html/_m_e_t_a_i_n_f_e_r_e_n_c_e.html" "This lesson teaches you how to perform and analyze Metadynamics simulations"
  click D "theory.html" "AlphaFold-Metainference theory intro & overview"
  click E "case_study.html" "Case study: TDP-43 monomer dyamics"
  click F "https://github.com/vendruscolo-lab/AlphaFold-MetaInference-Tutorial/blob/main/AF-IDP_colab.ipynb" "AF-MI colab performing software installation, system preparation, AF-MI simulation and post-processing analysis"
  click G "input.html" "Input: Protein sequence,  AF-MI simulation data and parameters"
  click H "postprocessing.html" "Structural ensemble generation and post-processing analysis"

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