1.1. What is Volsurf?

VolSurf is a computational procedure aimed to produce and to explore the physicochemical property space of a molecule (or library of molecules) starting from 3D maps of interaction energies between the molecule and chemical probes. The basic concept of VolSurf is to compress the information present in 3D maps into few numerical descriptors which are simple to understand and to interpret. Superposition of molecules is not required.

VolSurf is specifically designed for:

• In silico DMPK predictions

• ADME database analyses and filters determination for early phase drug discovery

• DMPK properties calculation to bias combinatorial libraries

• Pattern recognition techniques for specific ADME properties

• Fast generation of quantitative and lattice independent molecular descriptors for Quantitative Structure-Property Relationships

• Fast quantification on distribution, as well as magnitude of molecular surface polarity

• Extraction of chemical information from 3D molecular image maps

• Obtaining useful descriptors for optimizing pharmacokinetic properties in lead optimization

• Working with small, medium and large molecules, as well as with biopolymers (DNA, peptides and proteins)

VolSurf can be used for:

• Automatic generation of molecular descriptors designed for the computation of ADME properties

• Automatic ADME predictions for compounds database through Library models

• Lead optimization

• Importing data from GRID and/or Gaussian programs

• Generating useful quantitative 2D descriptors according to the input 3D maps

• Displaying Grid-maps together with the molecular structures and the generated descriptors

• Working with large batches of molecules in a single run

• Chemometrical analyses and external predictions

1.2. VolSurf descriptors and features

• Molecular size and molecular shape descriptors

• Hydrophilic and hydrophobic regions quantification

• Integy moments and Capacity factors

• Amphiphilic moment, Hydro-Lipo balance

• Non GRID descriptors: diffusivity, LogP, molecular elongation

• 3D visualization

• GRID input interface

• Gaussian input interface

• GOLPE output interface

• High quality PostScript, plotter and RGB bitmap (only for IRIX OS) output

• Command line interface

1.3. What VolSurf is not?

VolSurf is not a 3D converter program. Conversely, VolSurf uses the output of CONCORD or CORINA as input for MIF generation and image analysis processing. VolSurf is strictly linked to GRID force field that is used in VolSurf to generate the 3D input Molecular Interaction Field maps. VolSurf exports data ready to be processed by GOLPE chemometric programme.

1.4. Program citation.

The following citations are suggested when referencing the program:

1. G.Cruciani, M.Pastor, S.Clementi. Handling information from 3D grid maps for QSAR studies. Molecular Modeling and Prediction of Bioactivity. K. Gundertofte and F.E. Jørgensen (eds.) Kluwer Academic/ Plenum Publishers, New York 2000. pp 73-82

2. G.Cruciani, P.Crivori, P.-A.Carrupt and B. Testa. Molecular Fields in Quantitative Structure-Permeation Relationships: the VolSurf Approach. Journal of Molecular Structure: THEOCHEM 503, 17-30 (2000).

3. P. Crivori, G. Cruciani, P.-A. Carrupt and B. Testa. Predicting Blood-Brain Barrier Permeation from Three-Dimensional Molecular Structure. J. Med. Chem., 43 (11), 2204-2216, 2000.

1.5. Program organization

VolSurf has a Motif style graphic front-end. Commands are accessible using menus and dialog panels. The main VolSurf window looks like this:

From top to bottom we can see: the menu bar, the main text window and the status line (see Interface contents section).

• The menu bar contains all the commands of VolSurf. It is thoroughly described in this manual.

• The main text window is used by the program to shown text output. The contents of this window are written to a file with the extension .vol.Log

• The status line shows updated information about the data: Scaling applied, the number of objects, the number of X variables, the number of Y variables, and the probes used for the analysis.

Apart from this window, VolSurf can open many plots in separate windows. Plots are independent applications and can be moved, closed, minimized, etc... independently from the main front-end window.

1.6. Limitations.

The present version imposes no arbitrary limits to the size or to the number of molecules. However, the hardware and in particular the amount of RAM memory available might impose a limit.

1.7. User's support.

Molecular Discovery is committed to provide first quality user support to their customers. FAX and e-mail support is included in the price of the commercial licenses. Free academic licenses grant no user support.

Contact info are available in our website: http://www.moldiscovery.com.