Starts 19 Apr 2018 11:00
Ends 19 Apr 2018 12:00
Central European Time
ICTP
Leonardo Building - Luigi Stasi Seminar Room
Computational biology is playing an ever-increasing important role in understanding the atomistic level details of complex biological processes, rationalizing mechanisms and predicting novel aspects, which are inaccessible, yet complementary, to experiments and identify novel drugs to interfere with biological mechanisms leading to diseases’ onset. This field evolves extremely fast, so that microsecond/millisecond time-scale simulations are nowadays routinely performed to follow the dynamics of biological systems containing up to millions of atoms. In this talk, multi-scale simulations ranging from force field molecular dynamics to hybrid quantum-classical (QM/MM) simulations, in combination with free energy techniques, will enlighten the molecular mechanisms of complex biological processes ranging from (i) the splicing mechanism in self-splicing ribozymes up to the eukaryotic spliceosome [1,2], (ii) membrane–anchored enzymes metabolizing hormones [3], and finally, (iii) to signal transmission in nuclear receptors and their polymorphic variants [4].

[1] Casalino L., Palermo G., Rothlisberger U., Magistrato A. ‘Who Activates the Nucleophile in Ribozyme Catalysis? An Answer from the Splicing Mechanism of Group II Introns’ J. Am. Chem. Soc. (2016) 138 (33), 10374–10377 (Cover Picture)
[2] Casalino L., Palermo G., Abdurakhmonova N., Rothlisberger U., Magistrato A. ’Development of Site-specific Mg2+-RNA force field parameters: a Dream or a Reality? Guidelines from combined Molecular Dynamics and Quantum Mechanics Simulations’ J. Chem. Theor. Comput. (2017) 13 (1), 340-352
[3] Magistrato, A.; Sgrignani, J.; Krause, R.; Cavalli A.; Single or multiple access channels to the CYP450s active site? An answer from free energy simulations of the human aromatase enzyme. J Phys Chem Lett 2017, 8 (9), 2036-2042
[4] M Pavlin, A Spinello, M Pennati, N Zaffaroni, S Gobbi, A Bisi, G Colombo, Magistrato A A Computational Assay of Estrogen Receptor α Antagonists Reveals the Key Common Structural Traits of Drugs Effectively Fighting Refractory Breast Cancers Scientific reports 2018, 8 (1), 649