ACD/PhysChem Batch
What's New
Substantial developments to the PhysChem product line in version 11 include new and enhanced prediction models spanning all prediction models. Key new features of ACD/PhysChem Batch presented below are:
- A new model for logP prediction
- Enhancements to the pKa prediction model
- Automatic generation of ionic molecular forms
New Model for LogP Prediction
A new generation model for prediction of logP is introduced which combines data for ~12,000 compounds from ACD/Labs' internal training set with new experimental data from >13,000 pharmaceutical lead compounds. All internal fragments and incremental values were recreated using the new combined dataset. LogD and solubility modules are also impacted due the inclusion of logP in these prediction models.
NOTE: Both version 10 and 11 models for logP, logD, and solubility will be available for use in training and prediction.
Enhancements to pKa Prediction Model
Version 11 of the pKa model boasts the addition of >2,000 pharmaceutical lead compounds to the internal database. Analysis of the new subset of compounds along with a portion of the existing dataset generated over 600 new and revised Hammett equations. Improvements to the pKa model will have a significant effect on our logD and solubility modules since pKa is integral to these modules.
Automatic Generation of Ionic Molecular Forms
Automatically generate dominant molecular structures at defined pH values, and for specific ionized forms from Batch input files. Directly save the results as an SDfile.
Other improvements include:
- The option to include PSA with and without increments from bivalent sulphur in Rule-of-5 alerts
- The addition of eight new molecular descriptors that depict molecular composition
Changes to the Desktop Versions Included with PhysChem Batch
Numerous new features and improvements have also been made to the desktop products that correspond to the LogP, pKa, Solubility, and LogD Suite Batch applications. Some key features include:
- ACD/Quick Report-a new PhysChem interface that offers a snapshot of the molecular property profile of individual molecules
- Push data from Table View directly to Microsoft Excel at the click of a button
- Enhancements to training
For details on the new features in these applications please review the individual What's New documents for ACD/LogP DB, ACD/pKa DB, ACD/LogD Suite and ACD/Solubility DB.
Download a PDF copy of the expanded details on What's New with ACD/PhysChem Batch, or contact your Account Manager or Distributor.
The key features of ACD/PhysChem Batch presented below are:
- Enhancement of pKa, solubility, and logD algorithms
- Option to include contributions from bivalent sulfur in PSA calculations
- Enhancements to pKa System Training
Enhancement of the algorithms:
Version 10.0 development has addressed limitations of the fragment-breaking algorithm in pKa, solubility, and logD to allow the solubility profiles and these physical properties to be calculated for larger molecules and more complex structures (such as fused ring-systems). Fragmentation of molecules has now been focused around reaction centers (significant in the calculation of pKa upon which solubility and logD values can rely heavily) to minimize the number of fragments generated for a given system.
New option for PSA calculations:
Due to the sometimes problematic nature of bivalent sulfur, the option to include increments from this moiety has been added to allow you to obtain the most pertinent information from your calculations.
Enhancements to pKa System Training:
To allow greater flexibility in the application of User databases, you can now choose to simultaneously use fragments from both the user database (pkauser.dat) and the internal calculation database for calculation of pKa values. The default option to apply fragment increments from the User database first is also available.
Changes to the Desktop Versions Included with PhysChem Batch
Numerous new features and improvements have also been made to the desktop products that correspond to the LogP, pKa, Solubility, and LogD Suite Batch applications. Some key features include:
- Atom Numbering Consistency between User files and the History Window for all PhysChem products, particularly significant for pKa
- Expansion of the internal reference database in ACD/Solubility DB by >20%
For details on the new features in these applications please review the What's New in for ACD/pKa DB and ACD/Solubility DB.
Among the key new features of ACD/PhysChem Batch presented below are:
- Improvements in solubility prediction.
- Solubility training option with experimental solubility data.
- Improvements in pKa prediction for compounds with several ionization centers.
New fragment-dependent algorithm for solubility prediction
Introduction of a new algorithm resulted in the increase of the overall accuracy of solubility prediction, and the addition of a software training capability with the experimental solubility data. For more details, please review the What's New document for ACD/Solubility DB.
Higher accuracy of apparent EXACT pKa calculation for complex compounds with several ionization centers
Recent changes in the pKa calculation methodology resulted in the improved accuracy of pKa calculations for molecules with 3 or more ionization centers. The improvement is especially notable for compounds with ambiguous dissociation chains and close values of pKa microconstants for separate ionization centers.
For more details, please review the What's New document for ACD/pKa DB.
New pKa algorithm results in the improved accuracy of logD and solubility pH profiles and calculations outlining the distribution of ionic forms.
Additional improvements include:
- Calculation of all noticeable ionic forms at a given pH.
- Warning flags for inaccurate pKa.
ACD/PhysChem Batch, version 8.0, features significantly increased speed of calculation, and a new expert tool for pKa accuracy enhancement.
Considerably improved speed of calculation: the calculations are now four to ten times faster!
- Separate pKa, logD, and solubility calculations are sped up by four to ten times, while the whole set of property predictions is now about 10 times faster and is completed within seconds. In our recent test, pKa, logP, logD at 3 pH values, and solubility at 3 pH values for 10,000 compounds of pharmaceutical significance were predicted within an hour on a standard Windows Pentium IV 2.0 computer.
Review the latest calculation statistics and speed below:
Speed comparison for versions 7.0 and 8.0 of ACD/PhysChem Batch, expressed in structures per second.
(Total number of compounds in the test set: 400)
| Property |
Average speed, structure/second, v.7.10 |
Average speed, structure/second, v.8.0 |
Multi-fold increase in compute speed, v.8.0/v.7.10 |
Multi-fold increase in compute speed, v.8.0/v.7.0* |
| pKa (apparent) |
1.5 |
16.67 |
11 |
11 |
| LogP |
15.5 |
17 |
1 |
1 |
| LogD (pH) |
1.08 |
8.7 |
8 |
8 |
| Solubility (pH) |
0.9 |
3.88 |
4.3 |
4.3 |
| pKa+logP+logD+Sol |
1.0 |
3.31 |
3.3 |
10 |
* - Computation performed with the earlier 7.0 versions of PhysChem Batch (prior to 7.10).
Expert chemists can now use their own measurements to add new Hammett equations for their novel chemical classes through NEW ACD/pKa Accuracy Extender. These equations are automatically incorporated into algorithms of ACD/pKa Batch and other related products to enhance prediction for all analogs from the new class.
Quaternary ammonium salts are supported by the current version.
The ACD/Sigma Batch module is included in ACD/LogD Batch and ACD/LogD Sol Batch, version 8.0.
ACD/PhysChem Batch version 7.0 features:
- Improvements to the pKa prediction algorithm for compounds with a thioxophosphine (P=S) fragment and N-containing aromatic rings, resulting in the higher accuracy of calculations for pKa, logD, and Solubility.
- Expanded data import capabilities. You can import and export ACD/ChemFolder databases (*.cfd). Also, it is possible to import text files containing SMILES codes.
Exciting new features and options are available for ACD/PhysChem Batch 6.0:
- Separate tabs are added for Solubility and Sigma calculations.
- Under Solubility, which can be calculated with or without melting point data, you can now calculate Intrinsic Solubility, along with Solubility at a specified pH and the Solubility of your chemical in unbuffered water with the corresponding pH value.
- Sigma (Hammett electronic substituent constant) is calculated for selected fragments of your molecule or the substituents of your library. Either one SDfile, containing a list of substituents, or two SDfiles, describing the core molecule (scaffold) and the library, can be used to generate sigma values. Available for Windows users.
- PSA (Polar Surface Area) can be predicted under the logP module.
- Improved interface features higher customization and better input/output integration. For example, you can specify labels for the functional groups for pKa calculations or select SDfile fields.
- ACD/PhysChem Batch 5.0 now includes the calculation and output of macroscopic properties: chemical formula, molecular weight, percentage composition, molar refractivity, refractive index, molar volume, density and the parachor.
- Improved algorithms for the calculation of logP and logD for the following classes of compounds: alpha-amino acids, triazine derivatives, melamine derivatives, and 2-sulfanilamidothiazole derivatives. (See ACD/LogP DB.)
- The program allows the user to select the "Rule of 5" properties to be output:
- Improved algorithm for the prediction of aqueous solubility (see ACD/Solubility DB).
- Fully compatible with, and able to update to, ISIS/Base 2.2 *.DB, except in the case of macroscopic properties ("ChemSketch properties").
- Ability to calculate Boiling Point values at different pressure values, Vapor Pressure values at different temperature values, Flash Point and Enthalpy of Vaporization.
- Additional mode of pKa values calculation for all possible dissociation centers when the rest of the molecule is considered neutral, ("Single pKa").
- Calculation of pKa values at the required pH range.
- Determination of acidic and basic pKa values.
- Ability to define pKa values for most acidic and most basic dissociation centers at both full and confined pH range.
- Treat amides and/or sulfonic and sulfuric acids as ionizable/nonionizable for pKa values calculation.
- Treat amides and/or aliphatic alcohols as ionizable/nonionizable for LogD values calculation.
- Training system with pKa user database (*.pud) to calculate more accurate pKa and LogD values.
- Training system with LogP user database (*.lud) to calculate more accurate LogP and LogD values.
- Calculation of pKa, LogP, LogD, Solubility (S), Bioconcentration Factor (BCF), Organic Carbon Adsorption Coefficient (Koc), Boiling Point (BP), Vapor Pressure (VP), Flash Point (FP) and Enthalpy of Vaporization values at a single session and saving all the results to the same file.
- Checking whether the processed structures meet the "rule of 5" (Lipinski's rules).
- Restricting time for calculation of one compound.
- Saving calculated data to RDF file (in addition to DB, SDF and TXT files). The data in RDF file is organized in definite hierarchical order, that makes it possible to import results from RDF format to 32-bit ISIS Base database.
- Capability to create and store the "Options File", a text file containing user-specified switches for a calculation session.
- Ability to skip structures in the beginning of SDF file and start calculation from some user specified structure.
- Output of calculated data in table format.
|
