Towards faster drug design


Institutional Communication Service

31 July 2020

A powerful new computational tool to identify the most promising pharmacological compounds and thus allow a much faster "screening". That is what has been developed thanks to the research carried out by Prof. Vittorio Limongelli's group of USI Faculty of Biomedical Sciences in collaboration with Prof. Siewert Marrink's group of University of Groningen (Netherlands). Published in open access mode in the important international journal Nature Communications, the study outlines a method able to accurately simulate the interaction between a series of drugs and their biological "targets". 

The development of novel drugs - drug design, in technical jargon - is a complex activity, which requires a long and intensive research process. 


The development of novel drugs

The development of a new molecule able to interact effectively with specific biological targets, for a curative effect on the human organism, starts from the study of the targets themselves. The resulting information allows the development of the first test compounds, whose ability to bind with its molecular target is tested by computer simulations in order to identify those with the highest pharmacological potential, which are referred to as “lead compounds”. 

The process typically requires the preparation and analysis of an inordinate number of compounds, in the order of tens of thousands, in an operation called "screening". However, once the lead compounds have been identified, they are used to generate new active molecules, which are further tested and structurally modified to improve their ability to interact with their targets. The continuous iteration of new generations of pharmacological compounds continues until a small number of ideal candidates, usually less than five, are identified and are then sent for in vivo testing and, if positive, for human testing.


A new method to speed up drug development

The scientific work carried out by Prof. Vittorio Limongelli's team, in collaboration with Prof. Siewert Marrink's group, has led to identifying a new and effective computational method to speed up the "screening" phase.

Through the application of the molecular dynamics method and a new computational representation of the molecules, the two groups were able to simulate the interaction between a series of drugs and their biological targets with a level of precision comparable to that of other techniques already in use in the pharmacological field, but in a considerably shorter time. 

The method is both general and specific: in fact, it is a generalised molecular mathematical model, which replaces groups of atoms with “beads” having similar chemical-physical properties and which, however, makes it possible to correctly recreate the pharmacological capacities of specific compounds, distinguishing qualitatively and quantitatively the inactive molecules from the active ones, as well as identifying the differences in terms of efficacy between the latter.


A step forward and the chance for new perspectives

Such accuracy, combined with the method's speed of calculation, represents a significant step forward in drug design. The significant time reduction of the computational screening phase allows to speed up considerably the studies for the development of novel drugs, whose average duration today is 10-11 years. Moreover, this new technique could open new perspectives in the field of personalised medicine, thanks to the enhanced ability to analyse and test drugs and to their possible application in the development of drugs “tailored" on the characteristic of the patient.


Other challenges in computational pharmacology 

Prof. Limongelli's team, which operates within the Institute of Computational Science (ICS), is active on several research fronts in the field of computational pharmacology. Among other projects, also the one to achieve a faster way to detect among existing drugs those that can best fight COVID-19 (click here to learn more). 


Nature Communications is one of the journals of the Nature "family", one of the most authoritative and well-known names in the field of scientific publications. Nature Communications is an open-access journal; it publishes "high-quality studies", which "represent significant advances" in the natural sciences. The study by the group of Prof. Limongelli (USI) and the group of Prof. Siewert Marrink (Rijksuniversiteit Groningen) can be consulted at the following link: