Project E – MD modeling of YAP/TAZ mechanosensing

Objectives

The goal of this project is to build quantitative understanding of how mechanosensing by YAP and TAZ takes place. More specifically, the challenge is to connect the upstream interaction with the F-actin CSK to the critical inhibition events through the formation of protein complexes enabled by phosphorylation.

Description

Research in this project involves:

  • Unravelling the binding and conformational changes in YAP-protein complexes by Molecular Dynamics simulations, supplemented with NMR experiments.
  • Investigation of the binding of YAP to the transcription factor TEAD, which is known to enhance proliferation and to inhibit apoptosis.
  • Analyzing the critical binding sites and corresponding interactions by means of mutation studies. The resulting detailed molecular understanding may lead to the identification of residues outside the recognition sequences that could be potential targets for drug design.