Generating a molecular topology for an umbrella sampling simulation is just like any other simulation. Obtain the coordinate file of the structure of interest, and generate the topology from pdb2gmx. Some systems will require special consideration (i.e., protein-ligand complexes, membrane proteins, etc). For protein-ligand systems, please consult this tutorial, and for membrane proteins, I recommend this one on the topic. The principles of umbrella sampling are easily extendable to these systems, though we will consider only protein molecules in this tutorial.

The system we will consider here is the dissociation of a single peptide from the growing end of an Aβ₄₂ protofibril, and is based on simulations we recently published. The structure file of the wild-type Aβ₄₂ protofibril used in those simulations, acetylated at the N-terminus of each chain, can be found here. The original PDB accession code is 2BEG.

Run the structure through pdb2gmx:

gmx pdb2gmx -f 2BEG_model1_capped.pdb -ignh -ter -o complex.gro

Choose the GROMOS96 53A6 parameter set, SPC water, "None" for the N-termini, and "COO-" for the C-termini for each chain. Modify topol_Protein_chain_B.itp to include the following lines (at the end of the file):

#ifdef POSRES_B
#include "posre_Protein_chain_B.itp"
#endif

We will be using chain B as an immobile reference later on in the pulling simulations, hence the need to specially position-restrain this chain only, and none of the others.