Host: RCNS, Hungary (PhD enrolment at Budapest University of Technology and Economics)
Academic supervisor: Prof. dr. György M. Keserű (RCNS)
Researcher: Andrea Scarpino
Download the full description of this project: ESR8: Virtual Screening of Fragment Libraries of Covalent Binders
Computer-aided drug design (CADD) approaches are able to generate accurate molecular models that integrate available structural data with biochemical and biophysical screening data. In this project, we will develop computational chemistry protocols for modelling covalent protein binders and fragment hit evolution.
1.Designing a docking and scoring scheme for fragment sized covalent binders. These binding results will be complemented with reaction kinetic data. 2. Designing a computational protocol to extend the covalent fragments to covalent lead like compounds.
3. Virtual screening of commercially available reactive fragments against various proteins including Janus kinases.
4. Extending covalent binders that are identified by ESR3 and confirmed by ESR8 to lead like compounds
In this project, computational chemistry, molecular modelling, drug design and experimental technics to observe and quantify covalent binders will be combined. These studies will lead to computational methods to identify fragment sized covalent binders. It will also establish computational methods to extend covalent fragments to lead like compounds, e.g., for the identification of inhibitors of FragNet targets, including Janus Kinases (see ESR9).
Applicants must have experience with computational chemistry with a focus on molecular modelling. Familiarity with drug discovery concepts will be an advantage.
1. Singh et al. Nature. Rev. Drug Discov. 2011, 10, 307
2. Allen et al. Med. Chem. Commun. 2014, 5, 180.
3. Mah et al. Bioor. Med. Chem. Lett. 2014, 24, 33.