Automated docking of highly flexible ligands by genetic algorithms: A critical assessment
- 17 December 2003
- journal article
- research article
- Published by Wiley in Journal of Computational Chemistry
- Vol. 25 (3), 412-422
- https://doi.org/10.1002/jcc.10384
Abstract
An improved version of the fragment-based flexible ligand docking approach SEED–FFLD is tested on inhibitors of human immunodeficiency virus type 1 protease, human α-thrombin and the estrogen receptor β. The docking results indicate that it is possible to correctly reproduce the binding mode of inhibitors with more than ten rotatable bonds if the strain in their covalent geometry upon binding is not large. A high degree of convergence towards a unique binding mode in multiple runs of the genetic algorithm is proposed as a necessary condition for successful docking. © 2003 Wiley Periodicals, Inc. J Comput Chem 25: 412–422, 2004Keywords
This publication has 50 references indexed in Scilit:
- Designing screens: how to make your hits a hitNature Reviews Drug Discovery, 2003
- FlexE: efficient molecular docking considering protein structure variationsJournal of Molecular Biology, 2001
- The Protein Data BankNucleic Acids Research, 2000
- Continuum Electrostatic Energies of Macromolecules in Aqueous SolutionsThe Journal of Physical Chemistry A, 1997
- Molecular recognition of receptor sites using a genetic algorithm with a description of desolvationJournal of Molecular Biology, 1995
- X-ray Crystallographic Studies of a Series of Penicillin-Derived Asymmetric Inhibitors of HIV-1 ProteaseBiochemistry, 1994
- Rational Design of Potent, Bioavailable, Nonpeptide Cyclic Ureas as HIV Protease InhibitorsScience, 1994
- An alternative method for the alignment of molecular structures: Maximizing electrostatic and steric overlapTetrahedron Computer Methodology, 1990
- CHARMM: A program for macromolecular energy, minimization, and dynamics calculationsJournal of Computational Chemistry, 1983