ProBiS-Fold approach for binding site detection for whole structural human proteome in drug discovery

In the field of molecular modeling, we are involved with solving of various types of problems, such as, structure and dynamics of molecules, bulk matter research, chemical and biochemical reactions, and the development of new drugs. In this project, we will develop new methods for molecular modeling based on mathematical graph theory, a branch of mathematics that deals with discrete structures. Special attention will be placed on the development of new algorithms for predicting protein binding sites (ProBiS) and new web tools for modeling pharmaceutically interesting molecules - ProBiS Tools (algorithm, database, web server). The ProBiS Tools will be the first to allow the identification of interactions between protein structures, the prediction of ligand selectivity and binding, and the monitoring of the effects of conserved waters and sequence variants on ligand binding, to surpass human involvement in drug design. We will develop a new ProBiS-Fold approach, a catalog of binding sites and ligands for the entire human structural proteome. In ProBiS-Fold, binding sites will be categorized as proteins, compounds, ions, cofactors, nucleic acids or conserved water molecules. For each predicted binding site, ligands of the same type will be predicted based on the similarity of the binding site. ProBiS-Fold will provide interactive and downloadable binding sites for the entire human proteome, enabling both protein structure-function relationship studies and drug discovery across the entire structural human proteome. The ProBiS-Fold approach, on which the ProBiS-Fold web server is based, will enable for the first time interactions between most human protein structures not limited to the Protein Data Base structures only, prediction of selectivity and ligand binding, and observation of conserved water effects and ligand binding sequence variants. This work will provide the scientific community with a freely available, versatile server that researchers and clinicians can easily use from the web to detect molecules that bind to the proteins under their study. Our ProBiS tools will allow to combine several otherwise unrelated research areas, such as graph theoretical approaches, genetic variation studies, protein structure studies and molecular dynamics simulations. This project, which is at the forefront of current research trends in the field of molecular modeling, involves many researchers with outstanding scientific results and publications currently working in Slovenia and performing research work at the highest level. The field of computer-intensive methods and applications is an extremely propulsive field of scientific research, where the use of supercomputers and computer clusters solves the most demanding computational problems in theoretical and applied research in both natural and technical sciences. The development of new computational methods is closely related to the development of new algorithms and the development of modern computers. The project is clearly focused on the development of new molecular modeling methods used for targeted drug development, so the field of computer-intensive methods and applications is perfectly suited for this type of project.