MoMA LigPath


What is MoMA-LigPath
MoMA-LigPath is a web server that computes the exit path of a ligand from the protein active site to the protein surface. In the current version, flexibility is considered for the ligand and all the protein side-chains, and only geometric constraints are taken into account. Flexible protein backbone and energies will be introduced in subsequent versions. Note that cyclic ligands are not accurately treated yet (i.e. cycles are assumed to be rigid).
What are the inputs and outputs
The input is a .pdb file containing the coordinates of the protein-ligand complex. More than one ligand (or other molecules in addition to the protein, such as structural water molecules, ions, ...) can be considered. However, only the last ligand is considered to be mobile in the current version. Note that, although a cleaning/formatting pre-processing is applied to input .pdb files, we recommend the users to edit .pdb files for a manual pre-cleaning following the instructions below.
In the advanced use mode, an additional input file with extension .amc is required. This is an application-specific file format describing the flexibility of molecules (see explanations below).
The main output is a sequence of .pdb files corresponding to intermediate conformations of the molecules along the ligand exit path. Solution paths can also be visualized on the web by means of a Jmol applet.
In addition, an execution report provides information about possible errors in the input file and operations performed by the program.
How to use MoMA-LigPath
If you are a frequent user of the server, we recommend you create an account. This will enable you to access a record of the jobs you submit to the server, and to be informed about results by email. However, submitting jobs as an anonymous user is also possible.
There are two usage modes: simple mode and advanced mode.
The simple mode allows you to upload a .pdb file and edit a few parameters. MoMA-LigPath automatically generates the .amc file and proceeds with the job. This usage mode is sufficient in most cases.
The advanced mode offers more possibilities: you can edit more parameters and upload your own .amc file. The .amc generation tool For more information about this tool, read the section below provides you with a template file that you can modify.
How to clean/format .pdb files
Cleaning/formatting of .pdb files is required by MoMA-LigPath. In particular: molecules must be separated by TER records , and irrelevant molecules, such as non-structural water molecules, have to be removed. These operations are automatically performed in a pre-processing stage. Nevertheless, we recommend the users to edit .pdb files for a manual pre-cleaning in order to minimize mistakes. Special attention has to be paid to water molecules. The .pdb cleaning pre-process removes water molecules named HOH in the input file. If you want to keep some water molecules, please replace the residue name record by something different to HOH. Finally, when the model involves several ligands or other molecules in addition to the protein, the mobile ligand must be placed at the end of the file.
How to generate and edit .amc files
An .amc generator tool is available at the advanced mode. Given a .pdb file, it generates a template .amc file that can be modified with any text editor. The .amc file format used here is extremely simple. It contains blocks describing the flexibility of molecules. For a protein, the block contains one line per residue. Each line contains the residue type, the residue number and two binary values to define the backbone and the side-chain flexibility, respectively. A value of 0 means that all the dihedral angles of the backbone or the side-chain are fixed. A value of 1 means that they can freely rotate. Note that, in the current version, only the protein side-chains can be defined as flexible. For a ligand, the block contains one line for each rotatable bond. Each line contains the numbers of the four atoms involved in the dihedral angle and the bound values for the angle. You will find more information about the .amc file format in the file header itself.
How long should I wait for results
The simplicity of the molecular model together with the efficiency of the exploration algorithm applied by MoMA-LigPath permit the simulation of protein-ligand unbinding within very short CPU time, generally, from some seconds to a few minutes. However, waiting time can be significantly longer depending on the size of the stack of jobs submitted to the server. If you are a registered user, you will be informed by email when results will be ready. We suggest anonymous users to bookmark the results webpage (having a unique URL) for a subsequent access. Finally, note that MoMA-LigPath may fail to solve very geometrically constrained problems, which would require some flexibility of the protein backbone. This type of failure is indicated in the execution report, and the user is invited to resubmit the job with a reduced % of van der Waals radii.
Need more help?
For any other question, please contact us.