Prof. Michael Sattler (HMGU), Dr. Matteo Gentili (GIO), Dr. Grzegorz Popowicz (HMGU), Prof. Michael Nilges (IP)
Combining fragment-based screening and MCR.
About the project:
As an Early Stage Researcher (ESR) of the AEGIS consortium, the main aim of my doctoral studies will be that to develop new treatments against neglected diseases such as Chagas disease and the Sleeping Sickness. New methods based on a synergy of Computer-Aided Drug Design (CADD) and Structural Biology will be developed in order to improve predictions and thus reducing the time required for the Hit-to-Lead optimization phase. The structural information provided by physical methods such as NMR and X-ray crystallography will be used for Ligand- and Structure-based Drug Design. Multi-Component Reactions (MCRs) will be performed to synthesize the designed compounds.
This innovative approach to wet chemistry represents a powerful way to drastically reduce the chemical steps required by linear synthesis and thus the cost of the chemical assessment of the small molecules that undergo the Hit-to-Lead optimization process. Consensus computational methods such as Molecular Docking and Molecular Dynamics will be extensively used to exploit the data collected obtained from Structural Biology and biological assays. The main aim is to extend the amount of information that could be inferred from SAR and QSAR and to improve future predictions.
Roberto Fino, born 1984, is a Chemist specialized in Chemoinformatics and Organic Chemistry. He holds a Master Degree in Organic Chemistry from the Univesity of Bari, and since April 2015 until January 2016 he joined the Stefano Piotto's group Soft Matter Lab at the University of Salerno as a Fellow Researcher. During this time in the SML group he improved his skills in Python Scripting and how to master molecular modelling software such as YASARA Structure and Schrödinger Maestro. In cooperation with the other members of the SML, he developed and validate a new software for Molecular Docking called YADA (www.yada.unisa.it). Since April 2016 he started his PhD studies in the group of Prof. Michael Sattler (TUM/HMGU) under the supervision of Dr. Grzegorz Popowicz (HMGU) as ESR 2 in the AEGIS consortium.
ETH Zürich (1 month), University of Groningen (3,5 months)
List of publications:
Structure-Activity Relationship in Pyrazolo[4,3-c]pyridines, First Inhibitors of PEX14-PEX5 Protein-Protein Interaction with Trypanocidal Activity. Dawidowski M, Kalel VC, Napolitano V, Fino R, Schorpp , Emmanouilidis L, Lenhart D, Ostertag M, Kaiser M, Kolonko M, Tippler B, Schliebs W, Dubin G, Mäser P, Tetko IV, Hadian K, Plettenburg O, Erdmann R, Sattler M, Popowicz GM. J Med Chem. 2020 Jan 6. DOI:10.1021/acs.jmedchem.9b01876
List of posters:
Introducing the CSP Analyzer: a Novel Machine Learning-based Application For Automatic Analysis of Bidimensional NMR Data in Fragment-Based NMR Screen. Fino R, Byrne R, Softley C, Sattler M, Schneider G, Popowicz GM. New Frontiers in Structure-Based Drug Discovery, Sept. 23-25, 2019, Florence, Italy
Introducing the CSP Analyzer: a Novel Machine Learning-based Application For Automatic Analysis of Bidimensional NMR Data in Fragment-Based NMR Screen. Fino R, Byrne R, Softley C, Sattler M, Schneider G, Popowicz GM. Gordon Research Conference on Computational Aspects of Biomolecular NMR, Jun 9-14 2019, Les Diablerets, Switzerland
Elucidating the role of water molecules in Pex14-Pex5 PPI interactions; Fino R; HDDC 2018, Apr 26/27, Munich, Germany
List of presentations:
Combining NMR Fragment Screening and Multi Component Reactions in early Stage Drug Discovery; Pharmacy Day, June 2017
Institute of Structural Biology
Helmholtz Zentrum München
German Research Center for Environmental Health
Ingolstädter Landstr. 1