Il seminario si terrà il giorno 8 giugno 2023 - ore 11.00 presso l’aula 24 del Polo Scientifico Universitario di San Miniato
Il seminario fa parte dell’attività didattica del Dottorato di Ricerca in Scienze Chimiche e Farmaceutiche
Course schedule:
15/11/2022: Frontal lecture: Introduction to computer-aided drug design and main virtual screening approaches. 2 hours (15.00 – 17.00)
18/11/2022: Frontal lecture: Focus on pharmacophore-based and structure-based virtual screening, with case study analysis. 2 hours (15.00 – 17.00)
22/11/2022: Hands-on practice: students will perform a small virtual screening project that will include pharmacophore modeling, pharmacophore-based virtual screening, and structure-based virtual screening. 4 hours (14.00 – 18.00)
Lectures and hands-on practice will be delivered in person. For more information please contact: paolo.governa@unisi.it
Abstract
For centuries natural products have been the only source of bioactive compounds for therapeutic purposes. In the mid-1970s, they dominated the sources of novel human therapeutics in the pharmaceutical drug pipeline, particularly for cancer and infectious diseases. Indeed, two-thirds of the currently available drugs originated from unaltered natural products, their analogues, or contains natural products pharmacophores. Currently, about 200000 – 250000 natural products have been published, but it is estimated that less than 10% of the world’s biodiversity has been evaluated for its possible therapeutic application.
Despite being a proven source for modern small-molecule drug discovery, natural products also present challenges for drug discovery, such as technical barriers to isolation, characterization, screening, and optimization, which contributed to a decline in their pursuit by the pharmaceutical industry. Natural products, indeed, are often structurally complex, presenting several hydroxyl and ketones substituents and lots of chiral centers, and usually show high polarity and molecular weight, which make them unique and extremely diverse from synthetic molecules, but also very difficult to synthetize in large scale.
However, the advent of new technologies, such as improved analytical tools, genome mining and engineering strategies, microbial culturing advances, and computational methods now allows to focus on the most promising candidates, thus opening new opportunity for natural products in drug discovery.
In silico virtual screening is one of the most useful computational methods for filtering large database of natural compounds. Several virtual screening protocols could be applied to natural products libraries, including, but not limited to, cheminformatics, ligand-, pharmacophore-, and structure-based approaches, machine learning and molecular dynamics.
This course will cover aspects of pharmacophore- and structure-based virtual screening and will be divided into frontal lecture and hands-on practice.