Overview

SPROUT-HitOpt is specifically designed to aid in the hit optimization process of drug discovery.

There are two ways to perform hit optimization in SPROUT-HitOpt:

• Core Extension:
  Core extension allows you to explore different regions of a receptor's binding site by adding monomers to a core molecule. SPROUT-HitOpt uses a set of synthetic chemistry rules to identify "reactive functional groups" on a core molecule as possible extension points. At these extension points, monomers from a user-defined monomer library is systematically added to the core molecule to generate new compounds. Monomers are joined to the core structure via synthetic reactions.
• Monomer replacement:
  Monomer replacement uses retrosynthetic analysis to identify monomers within one or more bound ligands. These monomers are then replaced in combinatorial fashion by structurally related molecules taken from a monomer library to create new molecular structures.

Features

• Is a sopshisticated tool to optimize hit compounds
• 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
• Offers two modes of hit optimization: core extension and monomer replacement
• Provides tools to define your core molecule by importing a structure and modifying it
• Enables to generate your own customized monomer libraries
• In both modes, performs a systematic and exhaustive search to produce all the solutions that satisfy the steric constraints
• Core extension applies synthetic reactions to join monomers to the core structure
• Provides an option to perform the core extension 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 hit optimization. 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 review your results

Platforms

Supported operating systems:

• Linux
• Mac OS X