Seminar: Computational Studies of Biological Systems Related to Human Diseases

12/11/2018 - 12:00 - 13:00


Monday 12/11/18, 12:00 pm

Building 211, seminar room




Dr. Alessandra Magistrato

CNR-IOM at SISSA, Trieste. Italy




Computational Studies of Biological Systems Related to Human Diseases


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

[1,2,3], (ii) membrane–anchored enzymes metabolizing hormones [4,5], and finally, (iii) to signal transmission in nuclear receptors and their polymorphic variants [6].

[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] Casalino L., Palermo G., Soinello, A. Rothlisberger U., Magistrato A. All-atom simulations disentangle thefunctional dynamics underlying gene maturation in the intron lariat spliceosome Proceedings of the National Academy of Sciences, USA 201802963

[4] 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

[5] A Spinello, M Pavlin, L Casalino, A Magistrato A Dehydrogenase Dual Hydrogen Abstraction Mechanis promotes Estrogen Biosynthesis. Can we Expand the Functional Annotation of the Aromatase Enzyme? Chemistry–A European Journal 2018

[6] 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