How Far Are We from the Rapid Prediction of Drug Resistance Arising Due to Kinase Mutations?

About the Talk

Presenter

Mehmet Ergüven

Mehmet Ergüven completed his undergraduate studies in protein biochemistry (Department of Biochemistry, Ege University, İzmir) in 2016. He then carried out his master’s work in cell biology and computational structural biology at the İzmir Biomedicine and Genome Center. After finishing his MSc in 2019 he stayed on there for a year as a research assistant. He is currently pursuing a PhD in chemoenzymatic synthesis (Cells in Motion Graduate School, University of Münster, Institute for Biochemistry, Münster).

Abstract

Many protein kinases function in proliferative pathways. As a result, point mutations occurring in the ATP binding site of a kinase can lead to a constitutively active or drug-resistant enzyme, and ultimately to cancer. Because of technical and economic limitations, rapid experimental investigation of the effect of such mutations remains a challenge. This underlines the importance of protein–ligand binding affinity prediction tools that are ready to quantify the efficacy of inhibitors in the presence of kinase mutations. To this end, we compare here the performance of six web-based scoring tools (DSX-ONLINE, KDEEP, HADDOCK2.2, PDBePISA, Pose&Rank and PRODIGY-LIG) in assessing the impact of kinase mutations on their interactions with inhibitors. The results underline that there is room to improve the current scoring functions for predicting the effect of protein kinase point mutations on inhibitor binding.

Date: July 16th, 2021 – 6:00 PM (GMT+3)

Language: English