We describe a novel freely available web server Base of Bioisosterically Exchangeable Replacements (BoBER), which implements an interface to a database of bioisosteric and scaffold hopping replacements. Bioisosterism and scaffold hopping are key concepts in drug design and optimization, and can be defined as replacements of biologically active compound’s fragments with other fragments to improve activity, reduce toxicity, change bioavailability or to diversify the scaffold space. Our web server enables fast and user-friendly searches for bioisosteric and scaffold replacements which were obtained by mining the whole Protein Data Bank. The working of the web server is presented on an existing MurF inhibitor as example. BoBER web server enables medicinal chemists to quickly search for and get new and unique ideas about possible bioisosteric or scaffold hopping replacements that could be used to improve hit or lead drug-like compounds. BoBER web server is interactive and freely available at http://bober.insilab.org, and will benefit medicinal chemists in the lead optimization stage of the drug design process. The web server was tested in the Chrome and Firefox web browsers.
F.15 Development of a new information system/databases
COBISS.SI-ID: 6289946Ligand-based virtual screening of large small-molecule databases is an important step in the early stages of drug development. It is based on the similarity principle and is used to reduce the chemical space of large databases to a manageable size where chosen ligands can be experimentally tested. Ligand-based virtual screening can also be used to identify bioactive molecules with different basic scaffolds compared to already known bioactive molecules, thus having the potential to increase the structural variability of compounds. Here, we present an interface between the popular molecular graphics system PyMOL and the ligand based virtual screening software LiSiCA available at http://insilab.org/lisica-plugin and demonstrate how this interface can be used in the early stages of drug discovery process.
F.15 Development of a new information system/databases
COBISS.SI-ID: 5982490We developed LiSiCA (Ligand Similarity using Clique Algorithm) - ligand-based virtual screening software that uses a fast maximum clique algorithm to find two- and three-dimensional similarities between pairs of molecules and appliedit to the discovery of novel potent butyrylcholinesterase inhibitors. LiSiCA, which runs in parallel on multiple processor cores, was successfully tested on the Database of Useful Decoys - Enhanced, to evaluate its ability todiscriminate active molecules from decoys. We then applied LiSiCA for the discovery of novel inhibitors of human butyrylcholinesterase, a promising anti-Alzheimer target, using a known inhibitor as the reference compound. We demonstrated that LiSiCA is capable of finding potent nanomolar inhibitors, whose scaffolds differed from the reference compound, thus proving its abilityfor scaffold hopping and usefulness in drug discovery.
F.15 Development of a new information system/databases
COBISS.SI-ID: 3893361Prof. dr. Dušanka Janežič is regularly invited speaker at the American Chemical Society National Meeting & Exposition conferences. In recent years she gave invited talks at: 247th ACS national meeting and exposition : chemistry and materials for energy : March 16 - 20, 2014, Dallas, Texas 248th ACS National Meeting & Exposition : August 10-14, 2014, San Francisco, California 249th ACS National Meeting & Exposition, March 22-26, 2015, Denver, Colorado 250th ACS National Meeting & Exposition, August 16-20, 2015, Boston, Massachusetts 251th ACS National Meeting & Exposition, March 13-17, 2016, San Diego, California 253rd American Chemical Society National Meeting & Exposition, April 2-6, 2017, San Francisco, Clifornia 254th American Chemical Society National Meeting & Exposition, August 20-24, 2017, Washington, DC
B.04 Guest lecture
COBISS.SI-ID: 1536922564Finding: Impact of society •Women pay high price for success (choosing family or carrier). •Women cannot readily get a position without connections. •Family obligations impact status. •Conservative society. Success is measured in time not efficiency. •Women have to put much more effort and energy (sic to get ahead). •Leadership can have problems with maternity leave which lasts usually 1 year. •Lack of flexibility in jobs (working time, work from home) in Slovenia. •The greatest sexism in Slovenia is between females. Women do not support each other well enough; even women prefer to support men.
F.02 Acquisition of new scientific knowledge
COBISS.SI-ID: 1536940228