PyRx – Python Prescription

We have updated the PyRx website. Thanks to Joomla to WordPress plugin. Please open a support ticket if you find any broken links or missing information.

We are pleased to announce the release of PyRx 1.1. The following are new features included in this release:

• Machine Learning Scoring Function: Integrate the powerful RF-Score V2 machine learning scoring function to accurately assess docked poses or imported
• ADME Radar Chart: Create customizable radar charts that depict ADME-related properties for OpenBabel molecules, offering a holistic view of their molecules binding affinity.
• 2D-Structure Visualization: Explore the 2D-structure of the OpenBabel molecules along with a list of the associated properties and pharmacokinetic profiles
• Quick Filter: Simplify data analysis with easy-to-use min/max filtering options for docking results or OpenBabel molecules.
• Interactive Plotting: Customizable and interactive scatter plot and histogram for OpenBabel molecules
• Automatic Grid Box Centering: Optimize docking grid box positioning effortlessly by centering on a specific residue of the receptor. Enhance precision in molecular docking studies.
• Ramachandran Plot: Assess protein structure with an interactive and customizable Ramachandran plot. Gain valuable insights into the conformational quality of protein residues.
• Protein Structure Insights: Perform analyses on protein structure, including residue-type distribution, heteroatoms exploration, and more.

Features Details:

* Machine Learning Scoring Function: PyRx offers scoring of ligands using the RF-Score V2 scoring function, which is a machine learning scoring function with signficantly higher binding affinity prediction accuracy compared to the classical AutoDock and AutoDock Vina scoring functions. You can score docked poses from the results of AutoDock/AutoDock Vina docking process or ligands imported in the OpenBabel table. To score ligands (i.e. estimate binding affinity) towards a macromolecule using the RF-Score V2 scoring function, from the Scoring Menu, click Score Ligands, the score ligands dialogue will be opened.

Select the macromolecule (you can choose from molecules in Molecules Navigator) and the table of ligands to score. You can exclude heteroatoms from the macromolecule in the scoring process by checking the Exclude heteroatoms from macromolecule, which can be useful to exclude ligand and solvent atoms if present. The path to the “rf-score-vs.exe” executable should be also specified. After clicking Ok, the ligands will be scored and the result will be added as a column to the corresponding table. The values are the pK (the -log of the activity) calculated by the RF-Score V2 scoring function. Higher values indicate higher estimated activity.

* When selecting a molecule in the Open Babel widget, you can now see the 2D structure of the molecule.

Click the Details tab for the radar chart showing Molecular Weight, number of hydrogen bond donors (HBD), number of rotatable bonds (#Rots), octanol-water partition coefficient (LogP), and the number of hydrogen bond acceptors (HBA) in blue. The light green area shows where these values satisfy the Lipinski Rule of Five. You can also click on HBDs or HBAs checkboxes to highlight in Open Babel 3D viewer hydrogen bond donors in red and hydrogen bond acceptors in blue.

* Quick Filter: To filter the molecules table, click on the Quick Filter icon in the desired table (OpenBabel Tab or Autodock/Autodock Vina Analyze Results Tab). The Quick Filter dialogue shows the columns available for filtering. For each column you can check the Enable checkbox to include the column in the filtering process. Use the min/max sliders to determine the desired range of values. The min/max values are inclusive and the enabled filters are applied using AND operator. The results are applied directly on the table. When closing the Quick Filter dialogue, the table will be reset.

* Interactive Plotting: Click on the 2D-Plots tab to show scatter/histogram plots. Select the axes columns (X/Y for scatter plot, X for histogram) and the values of the OpenBabel molecules will be plotted. Click on the settings icon to customize the plot options such as marker color, size, etc. In the scatter plot, you can click on a point to select the corresponding molecule.


* Automatic Grid Centering: When setting up the grid box for docking (AutoGrid/Autodock Vina), you can center the grid on a residue of the selected macromolecule for the docking process. Click on the “Center on Residue” button, then select the desired residue and click OK, the grid box center will be set to the coordinates of the selected residue.

* Ramachandran Plot: To generate a Ramachandran plot for a protein molecule, from the Analysis menu, click Ramachandran Plot, then select the desired macromolecule (you can choose from molecules in Molecules Navigator). The Ramachandran plot will be generated for the selected protein. You can view the plot in the Ramachandran Plot tab. Each point represent a residue, you can click on a point to display the residue name and angles values.

* Protein Structure Insights: You view a report of a protein structure details, from the Analysis menu, click Protein Structure Details, then select the desired macromolecule (you can choose from molecules in Molecules Navigator). A result of the analysis will be displayed containing general information about the protein structure. Also, chain information, standard residue distribution, heteroatoms residues and water residues information will be displayed.

PyRx 1.1 New Features Video

We are pleased to announce the release of Dockamon – PyRx 1.0. This is a work in collaboration with CrescentSilico. Dockamon – PyRx is a structure-based drug design software package containing two integrated software programs: Dockamon and PyRx. Dockamon is software for scoring ligand docked poses using machine learning scoring functions. PyRx is molecular docking and virtual screening software. Major features of Dockamon include:

• Ligands Scoring: Score docked poses using a machine learning scoring function including RF-Score V2 and SVM-Score.
• Consensus Scoring: Combine scores from more than one scoring function to achieve better predictions.
• Protein-Ligand Interactions: Publication quality 2D and 3D interactive visualization of protein-ligand interactions. Customizable interactions options.
• Protein and Ligand Preparation: Prepare protein structures and ligands for docking, scoring or other molecular modeling tasks.
• Filtering & Substructure Matching: SMARTS and SMILES pattern substructure search, numerical and text-based filtering of the data.
• Other Features: Additional functionalities, including chemical spreadsheet capabilities, protein structure management, descriptor calculations, and conformer generation.

Please use the links below to order Dockamon – PyRx. Academic and Pro are the same version. Academic version is discounted for academics and nonprofits users.

We are pleased to announce the release of PyRx 1.0. PyRx is an award winning virtual screening tool used and loved by scientists worldwide. The following are new features included in this release:

• Added similarity search for the Vina and AutoDock Wizards to find similar compounds in PubChem. You can now right-click on any of the rows under the Analyze Results tab and select Find Similars in PubChem … This searches PubChem using Similarity search, downloads 3D conformers matching search results and opens it with the Open Babel widget.
  

• Double click on any of the rows in the Open Babel widget to open PubChem in the web browser matching the Title of the compound. For instance:
  https://pubchem.ncbi.nlm.nih.gov/#query=C20H30O5.

• On the Vina Analyze Results tab users can now save SMILES strings:
  

• For Vina Wizard, on the Run Vina page, when you click on Forward button, PyRx checks to see if there is a Vina output file already present (out.pdbqt) for each ligand. If you have already run Vina, it won’t run a new Vina job again. It instead adds the output to the Analyze Results page. This is useful when you have run Vina for a large number of ligands and would like to add additional ligands without running Vina for every ligand. Users can force PyRx to run Vina for each ligand by pressing Run Vina button.
  

• When screening a large number of ligands, you can now limit how many ligands to display in the Analyze Results page for Vina Wizard. This is for computers that don’t have enough memory to load all docking results at once. Use PyRx > Edit > Preferences… and check Limit Docking for GUI Analysis. You can also enter a number of top results to display. PyRx can now sort all results by predicted binding affinity and display only top results in the GUI to avoid running out of memory.
  For screening large libraries of ligands, it is best to use a High-Performance Computing (HPC) cluster with many CPU cores and have PyRx run on a server with large memory (RAM). If you don’t have a server with large memory, this option can be used to limit how many Vina outputs PyRx loads into memory.
  

The list of changes for all previous PyRx releases is available on our Blog. Please use our ticketing system to report bugs or request new features – https://sourceforge.net/p/pyrx/tickets. We hope you will enjoy this new version of PyRx.

PyRx has been recognized with the following awards by SourceForge:

Community Leader
Community Choice
Open Source Excellence
SourceForge Favorite

These honors are awarded only to select projects that have reached significant milestones in terms of downloads and user engagement from the SourceForge community. This is a big achievement, as PyRx has qualified for these awards out of over 500,000 open source projects on SourceForge.

We are looking for a co-founder to work on PyRx. Someone who knows Python and computational chemistry and can contribute to this project. If you are interested, please email your Resume to dallakyans@gmail.com. The screenshot below is from zoominfo. The numbers are not accurate, but nice to have.

We are pleased to announce the release of PyRx 0.9.9. This is the first release since COVID-19 pandemic. This pandemic showed how important open science is for fighting emerging diseases. Since the earlier days PyRx has been actively used to find treatment for COVID-19 and there has been numerous publications using PyRx to find potential drug candidates against COVID-19. Our free version passed 113k downloads worldwide. A screenshot below shows geographic distribution of these downloads with darker green counties having the most downloads (India, United States and China are in the top 3).

Here are the main changes for PyRx 0.9.9 release:

• In Analyze Results tab for AutoDock and Vina Wizard you can now delete multiple selected entries at once using Delete icon on the upper right corner. You can also save multiple selected entries as SDF file with right mouse click. Thanks to Prof. Cheol-Min Park for requesting this feature.

• In Open Babel widget, you can now open multiple molecules at once.
• Fixed slow exit on Windows.
• Removed Remote (Opal Web Services) execution mode since NBCR and its associated websites/services have been retired as of April 30, 2020.

The list of changes for all previous PyRx releases is available on our Blog. Check out also our Facebook page where we post latest video tutorials and links to PyRx related publications.

It has been more than 5 months since the last update. Remdesivir first identified in Coronavirus Drug Discovery Competition as a potential COVID-2019 treatment is now authorized for emergency use by FDA. This is the fastest drug I’ve seen to go from ideation to clinical use. Although, given the price and scarcity, I hope, steroids can be a better alternative.There are a number of publications using PyRx to find new drugs for Covid-19 treatment. Given the time it takes for a toxicity study of a novel drug, repurposing existing drugs seems a more feasible option.

The number of downloads has increased during the pandemic. There have been around 20k downloads year to date (9/5/2020) compared to 10k downloads for the same period last year. This pandemic also emphasized that PyRx can live long after I’m gone, which is a good thing.

I’m glad to report that PyRx has been used to win Coronavirus Drug Discovery Competition. Congratulations and HUGE THANK YOU to Matt O’Connor who used deep learning techniques for molecule generation and PyRx to evaluate binding affinities (https://github.com/mattroconnor/deep_learning_coronavirus_cure). He identified Remdesivir as a potential COVID-2019 treatment, which Sage Health will be donating to the Wuhan institute of Virology for further analysis.

Happy to see that the free version is still working on Windows (since 2011), unlike Mac version, that gives me nothing but headaches. We do not plan to increase the price of PyRx anytime soon and hope that our website and the store will remain online during these troublesome times.

As you may know, you can use Vina Wizard > Analyze Results page to load multiple Vina outputs (*_out.pdbqt). For AutoDock, if you have already gone through the wizard, produced dlg (docking log) files and want to load them again, you can go through the wizard again to load them. PyRx won’t run AutoDock and will load the results instead, if all dlg files are in their places. PyRx stores dlg files in subfolders and since a file browser won’t let you select multiple files from different folders, it’s not currently possible to load dlg files using a file browser.

I’ve created a new script to enable this. Download load_dlgs.py and use PyRx > File > Run Python Script or click on Python icon on the toolbar on upper left to open this file. It opens Choose Docking Log Files dialog where you can select multiple dlg files. Please note that some of the PyRx functions, such as recently introduced Show Interactions, won’t work and will through error messages if you load dlg files this way.