A new way to design medicine
Designed molecules at the protein binding site. The predicted binding pose of the designed molecule is marked in blue and the binding pose verified by a more accurate technique is shown in green
A team from the Faculty of Chemistry of the Warsaw University of Technology has developed a new medicine design procedure that can be applied when there is little experimental data available on the molecular mechanisms of a disease or ways to treat it. The developed procedure is the result of the work of student Stanisław Kulczyk and associate professor Dr. Mariola Koszytkowska-Stawińska.
The team used publicly available and free computer software.
The new procedure has two steps. The first stage is the preliminary design of new chemical molecules.
– We used the so-called de novo method (anew, from the beginning), which consists in designing a drug based on the structure of a protein interacting with it – explains Prof. Koszytkowska-Stawińska. – This allowed us to limit the amount of experimental data needed.
The team from WUT combined this method with another one using smaller, known structural fragments (fragment-based approach). Thanks to this, the design process was significantly accelerated.
– The second stage of the procedure is to give the pre-designed molecules the most beneficial properties from the point of view of their potential medical use – explains Stanisław Kulczyk. – We carried out this stage using our own computer algorithm, which was of fundamental importance in this process.
To construct this novel algorithm, the team from the Faculty of Chemistry used an intuitive sequence of performed actions.
The new procedure is of a general nature and may be particularly useful for the design of medicines against new diseases (e.g. against COVID-19 caused by the SARS-CoV-2 virus) or against so-called neglected diseases.
The results of the team's work were summarized in a scientific article entitled “Novel drug design framework as a response to neglected and emerging diseases” published in the Journal of Biomolecular Structure and Dynamics (DOI: 10.1080/07391102.2022.2110519). The new procedure was created as a result of the implementation of the "Szkoła Orłów” [School of Eagles] project, co-financed by the European Union under the European Social Fund.
