Development and optimisation of computational tools for drug discovery

The aim of my PhD project was the development, optimisation, and implementation of new in silico virtual screening protocols. Specifically, this thesis manuscript is divided into three main parts, presenting some of the papers published during my doctoral work. The first one, here named CHEMOMETRIC PROTOCOLS IN DRUG DISCOVERY, is about the optimisation and application of an in house developed chemometric protocol. This part has been entirely developed at the University of Palermo - STEBICEF Department - under the guide of my supervisors. During the development of this part I have personally worked on the tuning and optimisation of the algorithm and on the docking campaigns to obtain molecule conformaitons. The second part, THE APPLICATION OF MOLECULAR DYNAMICS TO VIRTUAL SCREENING, presents a new approach to virtual screening, in particular the attention is focused on different approaches to the application of protein flexibility and dynamics to virtual screening. This part, has been carried out in cooperation with the University of Vienna - Department of Pharmaceutical Chemistry. For these works I have worked in the development of the general workflow, to a lesser extent to the programming (coding) part of the applications used and I mainly focused on the realisation of the screening campaigns and results interpretation. The third and last part, COMPUTATIONAL CHEMISTRY IN POLY-PHARMACOLOGY AND DRUG REPURPOSING, concerns the study of the in silico methods applied to two main topics of the drug discovery process, such as the drug repurposing and the polypharmacology. In this part I will briefly describe what published in two reviews dealing to the above mentioned topics. In conclusion during this doctoral project, I have demonstrated how the use of in silico tools can be useful in the drug discovery process. The Chemometric protocols developed and optimised represent in fact a helpful strategy to use for target fishing. Whereas, the application of molecular dynamics to virtual screening, especially for pharmacophore modelling, is a new way to deepen crucial features to be adopted in the search of new putative active compounds.