OpenEye has announced the release of OEDocking v3.0.1. This is a bug fix release to the FRED, HYBRID, and POSIT programs. Of note, the report generated by both FRED and HYBRID has been significantly improved with this release
- The program dockreport has been renamed to DOCKINGREPORT
NEW FEATURES AND IMPROVEMENTS
- The formatting of the DOCKING_REPORT has been significantly improved and now includes:
- Added a protein interaction fingerprint
- Polar Surface Area (PSA)
- Improved the geometry detection for hydrogen bond protein constraints in FRED and HYBRID. These constraints should now be tighter.
- Stereo isomer detection in POSIT was not handling bridgeheads properly, this caused some non-stereo molecules to be identified as such.
- Fixed a bug in FRED and HYBRID where clash detection between hydrogen bonding groups was occasionally too strict.
DOCK is a suite of programs for molecular docking. In version 6.6 two new scoring functions are available: Grid-based footprint scoring and SASA-based scoring.
The MultiGrid Footprint Score calculates the pair-wise interaction energies over multiple grids. Important receptor residues are initially identified with a reference ligand, and individual grids are generated to model such residues.
The SASA score calculates the percent exposure of a ligand, and the percentage of the hydrophobic portion of a ligand and the receptor that are buried in the pocket.
In addition, a symmetry corrected RMSD (Hungarian matching) method was added to facilitate pose reproduction studies.
Full information on what is new in DOCK 6.6
CLC bio is pleased to announce a new release of Molegro Virtual Docker , an integrated platform for computational drug design available for Windows, Linux, and Mac OS X. Molegro Virtual Docker offers high-quality protein-ligand docking based on novel optimization techniques combined with a user interface experience focusing on usability and productivity.
New features in version 5.5:
A new 'Energy Maps' tool provides volumetric visualization of protein force fields. This makes it possible to understand why a compound interacts with a given receptor, and may provide insights on how to improve the binding.
We also added a new execution mode in the Docking Wizard: 'Run Docking in Multiple Processes'. This makes it possible to run medium sized jobs on a local machine, while utilizing multiple CPU cores and even multiple GPU graphics cards. For large jobs on multiple machines, Molegro Virtual Grid should still be used.
The ray-tracer has been improved to more closely match the live 3D view output. This makes it possible to create high resolution renderings of the 3D view.
Cresset have announced the formal release of sparkV10 the replacement for FieldStere.
- Updated molecular mechanics force field that uses a single analogue nitrogen atom and updates the field patterns for many functional groups including aromatic halides
- Added capability to read protein excluded volumes from pdb files
- Added new cluster algorithms for clustering of results
- Added option to edit reference molecules in the molecular editor
- Added capability to manage columns in the results table
- New optional module for scoring results using StarDrop models, this does not require access to a StarDrop server, simply place StarDrop model files in a directory and they automatically get used if you have the right license. The standard ADMET models that Optibrium have created are supplied but it works equally well with any models created by StarDrop.
- Added fragment import option in database generator
- Added capability to rescore all results against a 3D QSAR model using Forge or Torch
- Added capability to search databases for a particular fragment or substructure
- Added option to delete entire clusters from results
- Added depth cue to 3D window
- Added a GUI interface for selecting a portion of a molecule and writing command line arguments
- Cleaner GUI with improved buttons
Users should note:-
SparkV10 completely replaces Cresset’s previous “FieldStere” application. If FieldStere is currently installed then it is recommended to uninstall the binary to avoid confusion over which application should be used to open FieldStere project files
This is a review of ForgeV10 the latest offering from Cresset, whilst a new product those familiar with FieldAlign and FieldTemplater will recognise much of the functionality. ForgeV10 allows the scientist to use Cresset’s proprietary electrostatic and physicochemical fields to align, score and compare diverse molecules. It allows the user to build field based pharmacophores to understand structure activity and then use the template to undertake a virtual screen to identify novel scaffolds.
There is a compilation of software reviews here.
SZMAP uses semi-continuum Poisson-Boltzmann electrostatics to map variations in solvent properties in a protein binding site. It identifies key waters, shows their interactions, compares them to the corresponding ligand atoms, and determines whether neighboring waters aid or hinder binding. The newly released tool GAMEPLAN, suggests ways to modify ligand chemistry based on this understanding of water structure in the immediate environment of the ligand.
- The Water Orientation VIDA Extension has been completely rewritten to be easier to use and more feature-rich, making it simple to find key waters and understand their interactions. Each water site can be labeled by its energy, van der Waals energy, and degree of order. The 3D representation shows whether a site is disordered, an acceptor, a donor, or both. Individual waters can be exported for use elsewhere. The other extensions have also been improved.
- A new command-line program called GAMEPLAN has been released. GAMEPLAN runs several quick SZMAP calculations and analyzes the results to examine how the existing ligand chemistry aligns with the pocket environment. It also produces hypotheses of ligand modifications to improve its affinity, based on the energetics of the water environment directly adjacent to the ligand.
- SZMAP output has been simplified: sections are clearly identified, the water orientation data is less obtrusive, and an updated set of grids is produced (neutral difference free energy, van der Waals, order, and mask). The Watercolor VIDA Extension now sets contour levels to emphasize significant results.
- The speed of SZMAP stabilization calculations for both grids and arbitrary coordinates has been increased. Results from an existing apo protein calculation can be re-used, speeding up calculations for a series of compounds and/or poses in a single binding site. The speed of stabilization calculations is improved by avoiding extra calculations on the isolated ligand.
- It is now easy to produce SZMAP results for just the region in the apo pocket where water has been displaced by the bound ligand, clarifying the analysis of water in the apo protein.
- The programs SZMAP and GAMEPLAN will check to make sure input files contain partial charges and explicit hydrogens to avoid wasting time on meaningless calculations when the input is incorrect.
- Protein preparation is easier because PCH (which adds partial charges to molecules and separates protein from ligand) now provides more control over the process and can work around structures that contain unsupported elements. PCH can now split out waters into a separate file.
POSIT - Ligand guided pose prediction POSIT is designed to use bound ligand information to improve pose prediction. Using a combination of OpenEye approaches, including structure generation, shape alignment and flexible fitting, it produces a predicted pose whose accuracy depends on similarity measures to known ligand poses. As such, it produces a reliability estimate for each predicted pose.
The optimizer has been enhanced to produce better aligned structures in certain cases.
A memory leak in the optimizer was fixed, POSIT should now properly handle large streams of molecules. The -mcs flag is now turned off by default. In some cases, the mcs was taking far too long for no real benefit in pose prediction.
FITTED is a suite of programs to dock flexible ligands into flexible proteins. This software relies on a genetic algorithm to account for flexibility of the two molecules and location of water molecules, and on a novel application of a switching function to retain or displace water molecules and to form potential covalent bonds (covalent docking) with the protein side-chains.
The Suite includes many new features and implementations:
FITTED is a suite of programs (FITTED, PREPARE, ProCESS and SMART), JAVA GUI for easy keyword file editing and docking, Fully automated and flexible protein docking program, Automated covalent docking, Automatic protein preparation from pdb to mol2, Multi-mol2 support for docking and ligand processing, Uses an evolutionary algorithm, Semi-flexible protein docking with flexible waters, Has the ability to consider water molecules displaceable, Keyword files are simpler than ever, Support for Windows, Linux 32 and 64 bits, Mac OSX.
OpenEye has to announced the release of OEDocking v3.0.0. OEDocking is a suite of well-validated molecular docking applications (FRED, HYBRID, POSIT) and their associated workflows. This release features the official introduction of HYBRID, as well as a major upgrade to FRED.
POSIT - Ligand guided pose prediction FRED - Fast exhaustive docking HYBRID - Ligand guided docking
I was reading the announcements of new products from OpenEye and I thought I should update the listings.
AFITT from OpenEye is the only software to offer a fully automatic ligand fitting process that optimizes a real-space fit to density while keeping conformational strain to a minimum. It capitalizes on a combination of core technologies that OpenEye has developed, specifically conformer generation, shape potential, high quality small molecule structure minimization, and visualization. The key step, after finding the appropriate conformers and aligning them to density, is the implementation of a refinement that combines force field and shape potentials, via a series of adiabatic optimizations . The AFITT distribution includes both a GUI and a collection of command-line applications.
BROOD is a software application designed to help project teams in drug discovery explore chemical and property space around their hit or lead molecule. BROOD generates analogs of the lead by replacing selected fragments in the molecule with fragments that have similar shape and electrostatics, yet with selectively modified molecular properties. BROOD fragment searching has multiple applications, including lead-hopping, side-chain enumeration, patent breaking, fragment merging, property manipulation, and patent protection by SAR expansion.
FILTER is a very fast molecular filtering and selection application. It uses a combination of physical property calculations and functional group knowledge to remove undesirable compounds before they enter experimental or virtual screening. Undesirable properties may include: toxic functionalities, a high likelihood of binding covalently with the target protein, interfering with the experimental assay, and/or a low probability of oral bioavailability.
QUACPAC provides pKa and tautomer enumeration in order to get correct protonation states. It also offers multiple partial charge models (including MMFF94 , AM1-BCC , and AMBER ) that cover a range of speed and quality in order to allow appropriate charging for every end use. QUACPAC's approach to tautomeric enumeration is to provide multiple tautomeric states rather than one "correct" tautomer. Subsequent downstream processes are then used to identify the appropriate tautomeric form.
SZYBKI optimizes molecular structures with the Merck Molecular Force Field, either with or without solvent effect, to yield quality 3D molecular structures for use as input to other programs. Since the chemistry of molecular interactions is a matter of shape and electrostatics, it is impossible to consider either without reasonable 3D molecular structures. SZYBKI also refines portions of a protein structure and optimize ligands within a protein active site, making it useful in conjunction with docking programs.
I just heard about a platform - FORECASTER - that includes programs for drug discovery and process chemistry, these include
- FITTED, a docking program
- PREPARE, PROCESS and SMART, programs that can prepare protein and ligand files automatically
- CONVERT, a program that converts 2D molecules to energy-minimized 3D molecules (adds hydrogens, generates tautomers and protomers)
- SELECT, a program that computes compound similarity, extracts focused highly diverse libraries or identifies analogues
- REDUCE, a program that filters using descriptors and functionnal groups
- REACT, a program that performs combinatorial chemistry in silico from user-defined chemical schemes
- IMPACTS, a sites of metabolism prediction program (CYP 450)
- ACE, a program that predicts the stereochemical outcome of reactions
All the programs are integrated into a new web-based graphical interface that allows complete automation of the different workflows.
You can read more details here, Integrating Medicinal Chemistry, Organic/Combinatorial Chemistry, and Computational Chemistry for the Discovery of Selective Estrogen Receptor Modulators with Forecaster, a Novel Platform for Drug Discovery
CCG have announced the release of MOE 2011.10. This includes a new license manager compatible with LIon.
Some of the new and enhanced features in MOE include:
Non-Bonded Interaction Visualization Model - Visualize halogen bonds, H-bonds, CH-X, proton- for interactive modeling - Calculate strengths using Extended Hckel Model - Display strengths and interactions in 2D Ligand Interaction Diagrams Sequence Editor Redesign - Wrapped view, zoom, chain name/tag, etc. - Synchronized coloring (% identity, similarity, Clustal X, RMSD) - Cut and paste for loop grafting, inserting linkers, filling gaps, etc. Combinatorial Build in Pocket - Add R-groups to one or more attachment points in 3D pocket - Apply 2D and 3D filters, refine in (flexible) pocket and score - Use Builder to scan fragments for interactive ligand optimization Analysis of Solvent in Binding - Calculate within minutes a solvent binding free energy map using 3D-RISM - Calculate water, salt and hydrophobe solvation densities in complex or apo receptor - Diagnose how well alternate groups take advantage of water upon binding Macromolecular System Preparation - Correct common problems in protein structures automatically - Browse alternate conformations, cap termini, build missing loops - Optimize hydrogen bond network by flipping residues and adjusting states GPCR Family Database and Alignment Tools - Identify and annotate transmembrane regions of GPCRs - Add alignment constraints to improve GPCR sequence alignments - Augment a database of GPCR crystal structures with in-house data
Molegro is pleased to announce a new major release of Molegro Virtual Docker, an integrated platform for computational drug design available for Windows, Linux, and Mac OS X. Molegro Virtual Docker offers high-quality protein-ligand docking based on novel optimization techniques combined with a user interface experience focusing on usability and productivity.
Major new features in version 5.0: -GPU-accelerated docking on CUDA supported hardware making it possible to screen drug-like compounds up to 30 times faster than using conventional CPU-based methods. The GPU implementation builds upon and extends the research described in the paper "GPU-Accelerated High-Accuracy Molecular Docking using Guided Differential Evolution" (http://dl.acm.org/citation.cfm?id=2001576.2001818). -The new 2D Ligand Map provides an easy way to inspect and visualize protein-ligand interactions.
For more information, or to download a trial version, please visit our company website at: http://www.molegro.com
Molegro Virtual Grid creates an infrastructure for distributing docking runs on multiple machines. By simply installing the MVG agent on a computer, its resources can be used transparently by the grid controller. Virtual Grid support is built into Molegro Virtual Docker: for instance, to dock a library of compounds against a receptor, simply setup a compound data source, and select 'start job on Virtual Grid' in the Docking Wizard. Molegro Virtual Grid is multi-core aware and can be installed on any platform: Linux, Windows, and Mac. The machines in the grid do not need to run the same operating system. Now added to the alphabetical listing
The performance gains were very impressive, what was equally striking was the efficiency gains as measured by electricity usage, it looks like several thousand pounds will be saved for every million compound docking run.
He also showed the portability of OpenCL code, allowing efficient use of both the GPU and CPU.
He has a report on “The GPU Computing Revolution” available online
If you would like to learn more Apple have a OpenCL section in the Developer library, and Simon’s website is an invaluable resource, and there a couple of recommended books (links to Amazon)