2.1. New VolSurf descriptors

After long tests we are pleased to announce that 22 new descriptors have been added. The scope was to introduce a better measure for molecular shape and elongation, as well as for water diffusion property and water/octanol partitioning. They are explained more in detail below.

2.2. New library models

New Volsurf models have been added to the global library, which now contains nine useful models. The added models are:

• Biopharmaceutical classification

• Volume of Distribution

• hERG model

• Water/DMSO solubility model

• Metabolic Stability in CYP3A4

2.3. Improved library models

The BBB model was extended from 200 to 313 compounds; the Caco2 model from 400 to 800 compunds and the PB model from 300 to 400.

2.4. New way to handle library models

Two kinds of libraries (local or global) are now available: the User can decide where to locate the directories of local models and of global models. The former can be produced by the User and therefore can be easily saved, modified or expanded. The latter are provided by Molecular Discovery and can be used by the User for fast prediction of its own molecules.

2.5. Faster MIFs calculation

MIF computation speed has been significantly increased. A comparison with version 3 shows that the MIF generation is from two to three times faster, depending on the molecular geometry and size, while the entire MIF information is maintained.

2.6. Automatic Protonation-Deprotonation

The recognition of some chemically important groups has been automatised, with the introduction of an advanced option which allows the User to protonate-deprotonate groups such as NR₃/NR₃H⁺ and COO^-/COOH. Since the protonation of these groups depend on the pH, the User could define their protonation state without checking and modifying by hand hundreds of 3D-structures.

2.7. Handling of binary Vol files

VolSurf files may be easily handled. Starting from a .vol file, the User can expand the series (see the File->Expand series... command) or extract easily some compounds from a given list. In addition, two .vol files can be merged to a new .vol file without repeating the calculation, provided both were created using the same probes (see the File->Data file utils... command). The expansion or the contraction of .vol files can be also applied to library models, in order to build new libraries ( File->Model library...).

2.8. New method for charge distribution calculation

Starting from version 22 of GRID (May 2004) a new way to calculate atomic charges for HETATMs has been implemented: this method is now also available in VolSurf. Setting the charge preference (select AM1 near Charge computation method in the Preferences->Miscellaneus dialog) the atomic charges will be computed using a pseudoempirical Hamiltonian. The method is implemented for working on drug-like molecules: it can be applied only to HETATMs, with the limit of 100 HETATMs for molecule. In case the semiempirical method does not assign the charges to the whole molecule, Volsurf reverts to the default Saunderson algorithm. It could happen for a few reasons, such as when an atomic number not supported is found, or an open shell molecule is found, or the Self-Consistent-Field is not achieved.

2.9. Confidence interval

A confidence interval has been introduced in the 2D-PLS score plots, for an easier interpretation. The interval shown can be set by the User: for more info see Chapter 18.

2.10. Easier handling of large series of compounds

In order to deal with large series of compounds, two main features have been added. Under the "File Preferences" options the "delete" button was added for kout and pdb files, in case they are not cosidered by the User necessary after the calculation. In addition, all the files produced for the calculation (with the exception of the imported series) are moved to a new directory called .vol.Files which is automatically created.

2.11. More user settings

New options are available to set User's own preferences on sorted list, charge method, Grid-plot and browser for visualising the VolSurf manual in its HTML format.

2.12. User manual in pdf format

The VolSurf User manual has been totally reformatted. The most important headings linked to each other when required. The new pdf format has been added, with the intent to allow easy navigation and printing. Please help us to make a better job, and let us know if something is not clear or wrong in the text. Contact us at http://www.moldiscovery.com.