Description of the Project
The main aim of the Project was to examine the applicability and usage of Structural Interaction Fingeprints (SIFts) in the virtual screening tasks. Within the Project, there were developed tools supporting the evaluation of docking results and the search for optimal ligand conformation in the binding cavity. The representation of the ligand-receptor complexes obtained from docking by SIFts was combined with machine learning approach forming a semi-automated protocol for comprehensive docking results evaluation.
Moreover, on the basis of the interaction profiles formed by SIFts, a methodology of automated docking restraints assignment was developed. The SIFt profiles are used for quantification of the amino acids participating in the ligand binding and for selection of the most imporant contacts. Then, SMART patterns are assigned to the selected residues and they are used for prescreening of ligands and creation of the positional restraints for the most important amino acids.
Principal Investigator:
Stefan Mordalski, MSc
e-mail: stefanm@if-pan.krakow.pl
phone: +4812 66 23 301
Executors:
Krzysztof Rataj, MSc
e-mail: rataj@if-pan.krakow.pl
phone: +4812 66 23 301
Sabina Smusz, MSc
e-mail: smusz@if-pan.krakow.pl
phone: +4812 66 23 301
Jagna Witek, MSc
e-mail: jagna.witek@gmail.com
phone: +4812 66 23 301
Promotion:
a) publications:
- Witek, J.; Smusz, S.; Rataj, K.; Mordalski, S.; Bojarski, A. J. An application of machine learning methods to structural interaction fingerprints–a case study of kinase inhibitors. Bioorg. Med. Chem. Lett. 2014, 24, 580-585 (http://www.ncbi.nlm.nih.gov/pubmed/24374279)
- Mordalski, S.; Witek, J.; Smusz, S.; Rataj, K.; Bojarski, A.J. Multiple conformational states in retrospective virtual screening – homology models vs. crystal structures: beta-2 adrenergic receptor case study. J. Cheminform. 2015, 9, 7:13 (http://www.ncbi.nlm.nih.gov/pubmed/25949744)
b) participation in conferences:
- Mordalski, S.; Witek, J.; Rataj, K.; Smusz, S.; Bojarski, A.J.; A SIFt-guided approach to docking restrains assignment. An application to Virtual Screening; 5th Symposium of the Polish Bioinformatics Society, 25-27.05.2012, Gdańsk, Poland, Book of Abstracts, p.Talk10. Abstract Poster
- Mordalski, S.; Witek, J.; Rataj, K.; Smusz, S.; Bojarski, A.J.; Automated docking restrains assignment based on interaction profiles; GPCR Workshop 2013, 01-05.12.2013, Maui, Hawaii, USA, Book of Abstracts, p.54. Poster
- Smusz, S.; Mordalski, S.; Witek, J.; Rataj, K.; Bojarski, A.J.; A novel machine learning-based protocol for predicting biological activity of chemical compounds; GPCR Workshop 2013, 01-05.12.2013, Maui, Hawaii, USA, Book of Abstracts, p.58. Poster
The study is supported by a project “Diamentowy Grant” DI 2011 0046 41 financed by Polish Ministry of Science and Higher Education
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