From 9bdfe71daea5daec1f5939d49fe909fd1f053aa3 Mon Sep 17 00:00:00 2001 From: Irfan Alibay Date: Sat, 13 May 2023 17:22:04 +0100 Subject: [PATCH 1/4] Update cli_tutorial.md --- rbfe_tutorial/cli_tutorial.md | 36 +++++++++++++++++------------------ 1 file changed, 18 insertions(+), 18 deletions(-) diff --git a/rbfe_tutorial/cli_tutorial.md b/rbfe_tutorial/cli_tutorial.md index a39b593..10d1900 100644 --- a/rbfe_tutorial/cli_tutorial.md +++ b/rbfe_tutorial/cli_tutorial.md @@ -7,7 +7,7 @@ may need to use the Python interface for more complicated setups. The entire process of running the campaign of simulations is split into 3 stages; each of which corresponds to a CLI command: -1. Setting up the campaign creating files that describe each of the individual +1. Setting up the necessary files to describe each of the individual simulations to run. 2. Running the simulations. 3. Gathering the results of separate simulations into a single table. @@ -35,19 +35,20 @@ except that the RHFE planner does not take a protein. In this tutorial, we'll do an RBFE calculation. The only difference for RBFE is in the setup stage -- running the simulations and gathering the results are the same. -To run the command, we'll tell it get all the ligands from the SDF by giving -the option `-M tyk2_ligands.sdf`. You can also use `-M` with a directory, and -it will load all molecules found in any SDF or MOL2 file in that directory. -We'll tell the command to use the our PDB for the protein with `-p -tyk2_protein.pdb`. Finally, we'll tell it to output into a directory called -`network_setup` with the `-o network_setup` option. +To run the command, we do the following: + * Read all the ligands from the SDF by giving + the option `-M tyk2_ligands.sdf`. You can also use `-M` with a directory, and + it will load all molecules found in any SDF or MOL2 file in that directory. + * Pass a PDB of the protein target (TYK2) with `-p tyk2_protein.pdb`. + * Instruct `openfe` to ouput files into a directory called `network_setup` + with the `-o network_setup` option. ```bash openfe plan-rbfe-network -M tyk2_ligands.sdf -p tyk2_protein.pdb -o network_setup ``` Planning the campaign may take some time, as it tries to find the best -network from all possible transformations. This will create directory called +network from all possible transformations. This will create a directory called `network_setup`, which is structured like this: @@ -75,11 +76,11 @@ openfe view-ligand-network network_setup/ligand_network.graphml ``` This opens an interactive viewer. You can move the ligand names around to get a -better view of the structure, and if you click on the edge, you'll see the +better view of the structure, and if you click on the edge, you will see the mapping for that edge. -The files that describe each individual process we will run are located in the -`transformations` subdirectory. Each JSON file represents a single leg to run, +The files that describe each individual simulation we will run are located in the +`transformations` subdirectory. Each JSON file represents a single alchemical leg to run, and contains all the necessary information to run that leg. Note that this specific setup makes a number of choices for you. All of @@ -87,13 +88,12 @@ these choices can be customized in the Python API. Here are the specifics on how these simulation are set up: 1. LOMAP is used to generate the atom mappings between ligands, with a - 20-second timeout, element changes disallowed, and max3d set to 1. + 20-second timeout, core-core element changes disallowed, and max3d set to 1. 2. The network is a minimal spanning tree, with the default LOMAP score used to score the mappings. -3. Solvent is water with NaCl at an ionic strength of 0.15 M (neutralized). -4. The protocol used is OpenFE's OpenMM-based RFE protocol, with default settings. - - +3. Solvent is water with NaCl at an ionic strength of 0.15 M (neutralized) with a + minimum distance of 1.2 nm from the solute to the edge of the box. +5. The protocol used is OpenFE's OpenMM-based Hybrid Topology RFE protocol, with [default settings](https://docs.openfree.energy/en/stable/reference/api/openmm_rfe.html#protocol-settings). ## Running the simulations @@ -139,7 +139,7 @@ openfe fetch rbfe-tutorial-results tar xzf rbfe_results.tar.gz ``` -This will create a directory called `results/` that contains files in the file +This will create a directory called `results/` that contains files with the file structure you would get from running the calculations as above. The result JSON files are the actual results of a simulation. Other files that are generated during the simulation (such as detailed simulation information) have been @@ -182,7 +182,7 @@ failures that occurred -- these errors will not cause the entire campaign to fail, and will be recorded so you can later analyze what went wrong. To gather all the $\Delta G$ estimates into a single file, use the `openfe -gather` command from withing the working directory used above: +gather` command from within the working directory used above: ```bash openfe gather ./results/ -o final_results.tsv From 075b4adc85238f1239a58528e0f1fd6e9af9bdcf Mon Sep 17 00:00:00 2001 From: Irfan Alibay Date: Sat, 13 May 2023 18:45:19 +0100 Subject: [PATCH 2/4] more typos --- rbfe_tutorial/cli_tutorial.md | 5 ++--- 1 file changed, 2 insertions(+), 3 deletions(-) diff --git a/rbfe_tutorial/cli_tutorial.md b/rbfe_tutorial/cli_tutorial.md index 10d1900..0a43435 100644 --- a/rbfe_tutorial/cli_tutorial.md +++ b/rbfe_tutorial/cli_tutorial.md @@ -192,9 +192,8 @@ This will write out a tab-separated table of results, including both the $\Delta G$ for each leg and the $\Delta\Delta G$ computed from pairs of legs. The first column is a description of the data, e.g., `DGcomplex(ligandB, ligandA)` for the $\Delta G$ of the transformation of ligand -A into ligand B in vacuum, or `DDGbind(ligeandB, ligandA)` for the -$\Delta\Delta G$ of binding ligand A vs. ligand B: $\Delta G$bind, -$B$$ - \Delta G$bind$A$. The second column tells the type of +A into ligand B complexed to a protein, or `DDGbind(ligeandB, ligandA)` for the binding +$\Delta\Delta G$ going from ligand A to ligand B. The second column tells the type of the result, either `RBFE` for a relative result or `solvent`/`complex` for an individual leg. The next two columns are the labels of the ligands, and then the computed result and its uncertainty. From 13048635c305174f8b24d0372283b3535d2e6c90 Mon Sep 17 00:00:00 2001 From: "David W.H. Swenson" Date: Sat, 13 May 2023 13:57:48 -0400 Subject: [PATCH 3/4] Update rbfe_tutorial/cli_tutorial.md --- rbfe_tutorial/cli_tutorial.md | 2 +- 1 file changed, 1 insertion(+), 1 deletion(-) diff --git a/rbfe_tutorial/cli_tutorial.md b/rbfe_tutorial/cli_tutorial.md index 0a43435..6dee96d 100644 --- a/rbfe_tutorial/cli_tutorial.md +++ b/rbfe_tutorial/cli_tutorial.md @@ -93,7 +93,7 @@ how these simulation are set up: score the mappings. 3. Solvent is water with NaCl at an ionic strength of 0.15 M (neutralized) with a minimum distance of 1.2 nm from the solute to the edge of the box. -5. The protocol used is OpenFE's OpenMM-based Hybrid Topology RFE protocol, with [default settings](https://docs.openfree.energy/en/stable/reference/api/openmm_rfe.html#protocol-settings). +4. The protocol used is OpenFE's OpenMM-based Hybrid Topology RFE protocol, with [default settings](https://docs.openfree.energy/en/stable/reference/api/openmm_rfe.html#protocol-settings). ## Running the simulations From 205d860291ab4f3c3bafde1e20c3313dfaaadd13 Mon Sep 17 00:00:00 2001 From: "David W.H. Swenson" Date: Sat, 13 May 2023 13:57:53 -0400 Subject: [PATCH 4/4] Update rbfe_tutorial/cli_tutorial.md --- rbfe_tutorial/cli_tutorial.md | 2 +- 1 file changed, 1 insertion(+), 1 deletion(-) diff --git a/rbfe_tutorial/cli_tutorial.md b/rbfe_tutorial/cli_tutorial.md index 6dee96d..506adee 100644 --- a/rbfe_tutorial/cli_tutorial.md +++ b/rbfe_tutorial/cli_tutorial.md @@ -192,7 +192,7 @@ This will write out a tab-separated table of results, including both the $\Delta G$ for each leg and the $\Delta\Delta G$ computed from pairs of legs. The first column is a description of the data, e.g., `DGcomplex(ligandB, ligandA)` for the $\Delta G$ of the transformation of ligand -A into ligand B complexed to a protein, or `DDGbind(ligeandB, ligandA)` for the binding +A into ligand B complexed to a protein, or `DDGbind(ligandB, ligandA)` for the binding $\Delta\Delta G$ going from ligand A to ligand B. The second column tells the type of the result, either `RBFE` for a relative result or `solvent`/`complex` for an individual leg. The next two columns are the labels of the ligands, and then