title: OpenGrowth: An Automated and Rational Algorithm for Finding New Protein Ligands.
abstract: We present a new open-source software, called OpenGrowth, which aims to create de novo ligands by connecting small organic fragments in the active site of proteins. Molecule growth is biased to produce structures that statistically resemble drugs in an input training database. Consequently, the produced molecules have superior synthetic accessibility and pharmacokinetic properties compared with randomly grown molecules. The growth process can take into account the flexibility of the target protein and can be started from a seed to mimic R-group strategy or fragment-based drug discovery. Primary applications of the software on the HIV-1 protease allowed us to quickly identify new inhibitors with a predicted Kd as low as 18 nM. We also present a graphical user interface that allows a user to select easily the fragments to include in the growth process. OpenGrowth is released under the GNU GPL license and is available free of charge on the authors' website and at http://opengrowth.sourceforge.net/ .
authors.affiliation: Department of Chemistry and Chemical Biology, Harvard University , Cambridge, Massachusetts 02138, United States.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Chéron
authors.affiliation: Department of Chemistry and Chemical Biology, Harvard University , Cambridge, Massachusetts 02138, United States.
authors.forename: Naveen
authors.initials: N
authors.lastname: Jasty
authors.affiliation: Department of Chemistry and Chemical Biology, Harvard University , Cambridge, Massachusetts 02138, United States.
authors.forename: Eugene I
authors.initials: EI
authors.lastname: Shakhnovich
mesh_terms: D000465:Algorithms; D001331:Automation; D016333:HIV Protease / Q000737:chemistry*; D017320:HIV Protease Inhibitors / Q000737:chemistry; D008024:Ligands; D012984:Software; D014584:User-Computer Interface
chemical_list: D017320:HIV Protease Inhibitors; D008024:Ligands; D016333:HIV Protease; C514803:p16 protease, Human immunodeficiency virus 1