O. Korb, T. Stützle, T.E. Exner

 

In the drug development process, predicting the complex structure of a small ligand with a protein, the so-called protein-ligand-docking-problem, is extensively used in virtual screening of large databases and in lead optimization. Given a protein structure, a ligand structure and a scoring function, the goal is to find a low energy ligand conformation in the protein's binding site that corresponds to the global minimum of the scoring function. The docking algorithm PLANTS is based on a class of stochastic optimization algorithms called ant colony optimization (ACO). ACO is inspired by the behavior of real ants finding a shortest path between their nest and a food source. The ants use indirect communication in the form of pheromone trails which mark paths between the nest and a food source. In the case of protein-ligand docking, an artificial ant colony is employed to find a minimum energy conformation of the ligand in the binding site. These ants are used to mimic the behavior of real ants and mark low energy ligand conformations with pheromone trails. The artificial pheromone trail information is modified in subsequent iterations to generate low energy conformations with a higher probability.

 

PLANTS Features

  • ACO-based search engine
  • two scoring functions (PLANTSCHEMPLP and PLANTSPLP)
  • flexible protein side-chains
  • rigid-body docking of multiconformer libraries into rigid and flexible receptors
  • constraint system
  • docking with selected explicit, displaceable water molecules
  • fully automatic ligand setup (rotatable bond identification, atom typing ...)
  • virtual screening
  • rescoring capability

License Information

Versions for LINUX, Win32, and OSX are available here under a free academic license.
For a commercial copy please contact thomas.exner[at]uni-konstanz.de. To run the basic docking example, download a PLANTS version, unzip simple_dock.zip and run:
./PLANTS --mode screen plantsconfig
The docking output will be stored in the directory results

Structure Preparation

It is recommended to preprocess the protein and ligand input structures used for docking with SPORES.

User Interface

 

A graphical user interface able to generate PLANTS input scripts is available in Zodiac.

Collaborators

References

  1. PLANTS: Application of Ant Colony Optimization to Structure-Based Drug Design
    Korb, O.; Stützle, T.; Exner, T. E.
    Lecture Notes in Computer Science 4150, 247-258 (2006)
  2. An ant colony optimization approach to flexible protein-ligand docking
    Korb, O.; Stützle, T.; Exner, T. E.
    Swarm Intell. 1, 115-134 (2007)
  3. Empirical Scoring Functions for Advanced Protein-Ligand Docking with PLANTS
    Korb, O.; Stützle, T.; Exner, T. E.
    J.Chem.Inf.Model. 49, 84-96 (2009)
  4. NMR-guided Molecular Docking of a Protein-Peptide Complex Based on Ant Colony Optimization
    Korb, O.; Möller, H.; Exner, T. E.
    ChemMedChem 5, 1001-1006 (2010).

Studies using PLANTS

  1. Synthesis and Antiviral Activity of the Carbocyclic Analogue of the Highly Potent and Selective Anti-VZV Bicyclo Furano Pyrimidines
    Migliore, Marco D., Zonta, Nicola, McGuigan, Christopher, Henson, Geoffrey, Andrei, Graciela, Snoeck, Robert, and Balzarini, Jan
    J. Med. Chem., 50, 26, 6485 - 6492, 2007 linkout
  2. Functional and Structural Characterization of a Cation-dependent O-Methyltransferase from the Cyanobacterium Synechocystis sp. Strain PCC 6803
    Jakub Grzegorz Kopycki, Milton T. Stubbs, Wolfgang Brandt, Martin Hagemann, Andrea Porzel, Jürgen Schmidt, Willibald Schliemann, Meinhart H. Zenk, and Thomas Vogt 
    J. Biol. Chem., 283(30), pp. 20888-20896, July 25, 2008 linkout
  3. Indolylarylsulfones Bearing Natural and Unnatural Amino Acids. Discovery of Potent Inhibitors of HIV-1 Non-Nucleoside Wild Type and Resistant Mutant Strains Reverse Transcriptase and Coxsackie B4 Virus
    Francesco Piscitelli, Antonio Coluccia, Andrea Brancale, Giuseppe La Regina, Anna Sansone, Cesare Giordano, Jan Balzarini, Giovanni Maga, Samantha Zanoli, Alberta Samuele, Roberto Cirilli, Francesco La Torre, Antonio Lavecchia, Ettore Novellino and Romano Silvestri
    J. Med. Chem., ASAP, 2009 linkout

Publications referencing PLANTS

  1. Towards the development of universal, fast and highly accurate docking/scoring methods: a long way to go
    N. Moitessier, P. Englebienne, D. Lee, J. Lawandi and C. R. Corbeil
    British Jorunal of Phramacology (2008) 153, S7-S26 linkout
  2. Molecular docking with multi-objective Particle Swarm Optimization
    Stefan Janson, Daniel Merkle and Martin Middendorf
    Applied Soft Computing, Volume 8, Issue 1, January 2008, Pages 666-675 linkout
  3. Designing a ligand for pharmaceutical purposes
    Andrea Bortolato and Stefano Moro
    Expert Opinion on Drug Discovery, May 2008, Vol. 3, No. 5, Pages 579-590 linkout
  4. Free resources to assist structure-based virtual ligand screening experiments
    Bruno O. Villoutreix, Nicolas Renault, David Lagorce, Olivier Sperandio, Matthieu Montes and Maria A. Miteva
    Current Protein and Peptide Science, 2007, Vol. 8, No. 4, Pages 381-411 linkout
  5. The Influence of Mutation on Protein-Ligand Docking Optimization: A Locality Analysis
    Jorge Tavares, Alexandru-Adrian Tantar, Nouredine Melab and El-Ghazali Talbi
    Lecture Notes in Computer Science, 2008, vol. 5199, Pages 589-598 linkout