7th Structural Biology Club of the Czech Society for Structural Biology
26 January 2022, 1 pm
with the following scientific talks kindly delivered by our guests:
Predictive multi-scale mechanistic modeling for high-confidence drug target identification and treatment optimization
Presented by Tomas Helikar from University of Nebraska at Lincoln
Biological processes across organisms are governed by complex, nonlinear network systems that span multiple layers of biological organization, from molecular to cellular to organ and organismal levels. Mathematical and computational modeling has become integral to better understanding the systems’ mechanism and dynamics under healthy as well as diseased conditions. In this presentation, discussed will be our efforts in the development of a comprehensive host-pathogen computational model, depicting the infection of Influenza A of airway epithelial cells. Systemic simulations of the model identified novel host drug targets that have the potential to minimize viral replication. Results of our subsequent in vitro studies to validate these targets through combinatorial drug treatments suggest potential novel strategy for drug-based mitigation of influenza infection.
Structure-aided development of ligands targeting human prostate-specific membrane antigen
Presented by Cyril Bařinka from Institute of Biotechnology, Czech Academy of Sciences, Vestec near Prague
Prostate-specific membrane antigen (PSMA) is a transmembrane glycoprotein overexpressed in prostate carcinoma (PCa). As it serves as a biomarker for the imaging and therapy of PCa in clinic, the development of PSMA-targeting ligands is actively pursued in the field. We have designed and characterized in detail new molecular rotor probes with picomolar affinity for PSMA. Structural characterization of the PSMA/probe complex provided mechanistic rationale for the fluorescent enhancement upon PSMA binding. In vitro and ex vivo experiments using PCa cell lines and clinical samples, respectively, indicate the utility of the probe for biomedical applications, including real-time monitoring of endocytosis and tumor staging.
Please, join us on this Zoom link (join 5-10 minutes before the beginning)
Meeting ID: 934 8283 6889