Overview

SPROUT is an effective tool for the design of drug-like, biologically active molecules. It is an interactive system that can assist in several stages of the structure-based rational drug design process.

The system is modularised and offers automatic methods for solving a number of problems in drug design. The user maintains control and is able to guide and modify each module for maximum versatility.

The individual modules serve the following functions:

• Binding pocket identification in the solvent accessible surface of the protein complex
• Identification of favourable hydrogen bonding, metal bonding and hydrophobic regions or target sites within the binding pocket
• Docking of functional groups to target sites to form starting fragments for structure generation
• Fragment joining to build skeletons from the starting groups by satisfying the steric constraints of the binding pocket
• Scoring and sorting the solutions on binding affinity, complexity anaysis to estimate synthetic feasbility, searching for substructures

Features

• Is a sopshisticated de novo software tool
• Opens the crystal structure of target molecules in PDB format
• Has an advanced 3D graphical visualisation tool for displaying the detected target site regions, the generated structures, the protein receptor and the boundary surface
• Provides incredible control via
  • various parameters to guide the structure generation process, the size and shape of target sites, the docking of structures into the cavity and target sites, etc.
  • the ability to select building fragments, target sites, etc.
  • the facility of importing and editing molecules to define your core structures
• Generates structures from fragments via new-bond, spiro and ring fusion joins
• Performs a systematic and exhaustive search to produce all the solutions that satisfy the steric constraints and the adjusted parameters
• Applies a bidirectional search to tackle the combinatorial explosion during the exploration of large search spaces
• Represents the search space and the target site regions continuously rather than as a set of discrete points
• Provides an option to perform the structure generation process remotely on a cluster by distributing the search among nodes
• Offers tools to help you select the structures of your interest based on
  • binding affinity scores
  • structural complexity scores
  • substructure search
• Saves the results into PDB, MDL SDfile and Postscript formats
• Supports multi-session ligand design. This can be done by saving the results into SPROUT's internal file format which can be reloaded at a later time in order to continue designing new structures

Platforms

Supported operating systems:

• Linux
• Mac OS X