Protein-protein arayüzlerini yeni yaklaşım PROT-ON algoritması ile yeniden tasarlanması

Many biological activities in the body are mediated through protein-protein interactions (PPI). Understanding the PPIs is crucial for developing vaccines and drugs. Therefore, it is of utmost importance to understand how interfacial mutations change the nature of protein-protein interactions. To understand this phenomenon, several computational approaches such as FoldX and EvoEF have been developed. These tools estimate the change in the interaction energy by using different mathematical algorithms. In this thesis, by making use of these programs, we developed PROT-ON, which can scan all the interfacial mutations to explore the mutational landscape of a protein-protein interface. PROT-ON then classifies the mutations as most depleting or enriching, based on several metrics. We tested PROT-ON on MDM2-p53 and AXL-GAS6 complexes. For these cases, our approach was able to predict mutations that are critical to the vitality of the complex. The standalone version of PROT-ON can be cloned for Linux and macOS systems from GitHub (https://github.com/CSB-KaracaLab/prot-on) or can be accessed through a user-friendly web server (http://proton.tools.ibg.edu.tr:8001).