Protein binding sites are functionally important regions on protein surfaces, through which proteins interact with other molecules, such as drugs. Sequence variants are variations in a single nucleotide that occur at a specific position in the genome and can alter proteins, sometimes resulting in dysfunctional proteins causing various diseases and changing individual's response to drugs. This proposal will focus on the development and use of computational methods at the molecular scale for precision medicine to detect binding sites and to map sequence variants to binding sites. With such new approaches we will investigate how sequence variants change properties of binding sites.
Further, our aim is to include protein flexibility to improve the scoring of the binding affinity by using enhanced molecular dynamics simulations. This will be aided by vibrational modes to define the essential coordinates of the binding site movements. To disseminate our methods and reach higher impact, special emphasis will be given to sharing the newly developed computational methods with the community by making them easily accessible through a web-based interface and server. The proposed project's contribution will be a new computational tool for precision medicine, enabling prediction of changes in drug binding due to sequence variants. Discovery of these sequence variants is important and will have wide implications for research and generation of new hypotheses in medicine and drug discovery.
Project leader on the Slovenian side
National Institute of Chemistry, Slovenia
University of Ghent, Belgium
Slovenian Research Agency (ARRS)
Research Foundation – Flanders (FWO)
1.07 Computationally intensive methods and applications
Duration of the project