Proteins interact with other molecules through their protein binding sites, which are functionally important regions on the protein surface. Each binding site usually binds one or more specific molecules called ligands. A ligand can be a metal ion, a water molecule, another protein, a nucleic acid, or a small molecule. Detection of binding sites provides information about protein functionality and is therefore essential for drug development.<br/>The recent release of the AlphaFold protein structure database represents a major breakthrough in structural biology. It provides the scientific community worldwide with highly accurate structure predictions for 20,000 human proteins and proteins from 20 other biologically relevant organisms. However, the protein-only predictions in the AlphaFold database mean that protein-ligand interactions, such as interactions with other proteins, nucleic acids, drugs, cofactors, and co- and post-translational modifications, are missing. Knowledge of these interactions and their binding sites would allow functional and drug discovery studies to be performed on an unprecedented scale across the human proteome, such as structure-based virtual screening of the human proteome or prediction of the selectivity of new drug candidates compared with bacteria.<br/>We have developed such a system as part of our computational tools - ProBiS tools - that enables drug discovery based on protein structures from the AlphaFold database.<br/>Our newly developed approach is particularly useful in the context of precision medicine. Our tools allow linking different research areas that are otherwise not connected, e.g. genome sequence studies, protein structures and MD simulations.

Computational protein binding site tools at the scale of proteomes for protein-ligand binding in drug discovery

Fall 2022 abstracts, posters, and presentations will launch in mid-September.

ACS Fall 2022

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.