From molecular docking to virtual screening approaches: an in silico journey poking around the recognition event

Il 07/07/2017 ore 14.30 - 15.30

Sala Conferenze Cnr, Area della Ricerca Na1, via P. Castellino,111 80131 Napoli

Prof. Giulio Vistoli, from The Department of Pharmaceutical Sciences 'Pietro Pratesi', Faculty of Pharmacy, University of Milan,will give a seminar on docking simulations.

Docking simulations are very popular approaches able to assess the capacity of a given ligand to interact with a target. Docking simulations are usually focused on a single best complex even though many studies showed that ligands retain a significant mobility within a binding pocket by assuming different binding modes all of which may contribute to the monitored ligand affinity. The present lecture describes the fruitful opportunity of using score averages or weighted averages to simulate the synergistic role of ligand tautomers or of ligand ionization states as well as to account for the specific role of different protein states. More generally, the use of average score leads to an innovative concept, the binding space, which allows an exploration of the ligand mobility within the binding pocket by simultaneously considering several ligand poses as generated by docking simulations. The multiple poses and the relative docking scores can then be analyzed by taking advantage of the same concepts already used in the property space analysis; hence the binding space can be parameterized by (a) mean scores; (b) score ranges and (c) score sensitivity values. The first parameter represents a very simple procedure to account for the contribution of the often neglected alternative binding modes, while the last two descriptors encode the degree of mobility which a given ligand retains within the binding cavity (score range) as well as the ease with which a ligand explores such a mobility (score sensitivity). Along with examples of the above defined property space, the lecture will finish discussing a successful case of docking-based virtual screening analyses performed with a view to finding novel and potent muscarinic allosteric ligands.

Giulio Vistoli was born in 1968. He received his Laurea degree in medicinal chemistry at University of Milan in 1994. During his PhD studies with Prof. L. Villa, he spent a period in Lausanne under the supervision of Prof. B. Testa with which he has fruitfully collaborated since 1996. In 1999, he became Assistant Professor in medicinal chemistry at University of Milan, to be promoted to Associate Professor in 2010. In 2017, he obtained the Italian national habilitation for a Full Professorship in medicinal chemistry. His expertise involves the computational approaches as applied to pharmaceutical sciences in their broadest sense ranging from homology modeling and virtual screening to ADME predictions or drug delivery optimization. His recent researches focus on the development of new docking approaches to be used in both correlative analyses and virtual screening campaigns as well as in the rational design of selective and bioavailable scavengers of reactive carbonyl species. He is co-Author of more than 130 scientific publications. 

 

Organizzato da:
Ibp-Cnr

Referente organizzativo:
Andrea Beccari
Cnr - Istituto di biochimica delle proteine
a.beccari@ibp.cnr.it
081/6132339

Modalità di accesso: ingresso libero