Build Flow¶

The system preparation (‘building’) is a preliminary step to be able to perform Molecular Dynamics (MD) simulations. This is not always a trivial task especially considering that each force field (FF) has their own format files.

The systems can contain multiple molecules such as proteins, organic molecules (ligands, cofactors, etc), lipids and ions. Furthermore, the building process has to handle the solvation of the system and the placement of ions to reach the wished ionic strength.

The Build Flow is a workflow was designed to deal with all these variables and, when necessary, taking decisions for the user. Take into account that the design of this Flow was centered on the research of proteins (globular or membrane) with or without small molecules, in the context of studying drug design targets or performing in-silico binding assays. To summarize, this Flow can build system taking into account:

• Forcefield: Amber or CHARMM

• Salt concentration (Na+/Cl-)

• pH

• Proteins:
• with phosphorylated residues
• with more than 150 post-translational residues (Amber only)
• Ligand molecules (the parameters and topology need to be provided in the right format)
• in their original position
• at a random position (for membrane systems, only in the outer-membrane cytosolic)
• Membrane (the membrane file in pdb format need to be provided).
• the flow can also automatically align the protein structure to a structure retrieved from the ‘Orientations of

Proteins in Membranes’ (OPM).

Examples¶

Get the data for running the Build flow examples here. Unzip and untar it and follow the next examples.

There, four input folders for building can be found: two for Amber and two for CHARMM.

Build a Globular Protein system for CHARMM

To build a system consisting of a globular protein in water using the CHARMM force-field, use the following command:

aceflow Build --inputdir build/charmm/globular --builddir test_charmm_globular --forcefield charmm


Build a Membrane protein for CHARMM

To build a system consisting of membrane protein with a ligand placed randomly in the outer-membrane environment using the CHARMM force-field, use the following command:

aceflow Build --inputdir build/charmm/membrane --builddir test_charmm_membrane --forcefield charmm --pdbid 4eiy --membrane step5_assembly2.pdb --ligand ligand.pdb


Build a Globular Protein for Amber

To build a system consisting a globular protein with a phosphorilated residue (phopshorilated serine SEP) in water using the Amber force-field, use the following command:

aceflow Build --inputdir build/amber/globular --builddir test_amber_globular --forcefield amber


Build a Membrane Protein for Amber

To build a system consisting of a membrane protein with a ligand that we will be placed randomly in the outer-membrane enviroment using the Amber force-field, use the following command:

aceflow Build --inputdir build/amber/membrane --builddir test_amber_membrane --forcefield amber --pdbid 4eiy --membrane step5_assembly2.pdb --ligand ligand.pdb