...defining the field

What is ALMOND?

ALMOND is a program specifically developed for generating and handling GRIND descriptors (1). These are a new generation of molecular descriptors with applications in QSAR, virtual screening, design of combinatorial libraries and in general in any field where is needed a fast and accurate description of the molecular structure.

GRIND descriptors are describe in detail in the background section. Some of their most interesting properties are:

• Alignment independent.
• Based on Molecular Interaction Fields and pharmacophore concepts.
• Highly relevant with respect to the biological and pharmacological properties of the compounds.
• Fast to compute and compact to store.
• Interpretable with the help of interactive graphic tools.

GRIND descriptors are based on Molecular Interaction Fields (MIFs). ALMOND now integrates the program GRID (2,3) to generate the MIFs. This integration avoid the disk handling of GRID MIF, saving a lot of computing time. The simplest input for ALMOND are series of 3D molecular structures in standard file formats (sets of mol2 files, SDFiles, etc...). Alternatively, ALMOND can import pre-computed MIF from a variety of sources.

ALMOND includes a full package of chemometric tools specifically adapted to the GRIND descriptors. The package includes Principal Component Analysis, Partial Least Squares, FFD variables selection, PLS Model validation, External PLS and PCA predictions, etc... as well as a large variety of 2D and 3D interactive plots for helping in the interpretation of the models.

ALMOND is a real research tool, designed to be fast, simple to use, and highly flexible.

What ALMOND is not?

ALMOND chemometric tools can be applied only to the GRIND descriptors generated by the program. If you are looking for general purpose chemometric software we recommend the programs GOLPE and SIMCA.

ALMOND is not able to make CoMFA nor any CoMFA-like analysis. If you are interested on applying CoMFA on your series you first need to obtain a license from TRIPOS Inc.. CoMFA is a patented methodology.

Program organization

ALMOND has a Motif style graphic front-end. Commands are accessible using menus and dialog panes. The main ALMOND window looks like this (the aspect migh be slightly different for the SGI and Linux versions and depending upon the desktop configuration):

From top to bottom we can see: the menu bar, the main text window and the status line.

• The menu bar contains all the commands of ALMOND. 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 also written to a file with the extension .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, ALMOND 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.

Software and hardware requirements.

CPU

ALMOND 3.3.0 runs on :

• SGI workstations with MIPS III CPU's and version 6.5 of the IRIX operative system.
• PC with Intel processors running the Linux operative system version 2.4. ALMOND has been thoroughly tested on RedHat version 7.1 and higher but it is not guaranteed to work on other distributions of Linux.

Software

In order to see on-line help, any HTML browser should be installed and accessible.

Disk space

A full installation of all the programs, this manual and the tutorial files usualy requires less than 15 Mb of disk space.

RAM

For small and medium size molecules 64Mb of RAM are enough. For handling more complex molecules we strongly recommend the use of 128Mb or more.

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.

User's support.

Molecular Discovery Ltd. 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, but questions may be addressed in the proper section of our community forums available to all Molecular Discovery Users

References

1. M. Pastor, G. Cruciani, I. McLay,S. Pickett and Sergio Clementi. Grid Independent Descriptors (GRIND). A Novel Class of Alignment-Independent Three-Dimensional Molecular Descriptors. J.Med.Chem.43, 3233-3243 (2000).
2. P.J. Goodford, A computational procedure for determining energetically favourable binding sites on biologically important macromolecules, J.Med.Chem., 28, 849-857 (1985).
3. GRID v.22 Molecular Discovery Ltd., http://www.moldiscovery.com.