PT  - JOURNAL ARTICLE
AU  - Junk, Philipp
AU  - Kiel, Christina
TI  - Structure-based prediction of Ras-effector binding affinities and design of ‘branchegetic’ interface mutations
AID  - 10.1101/2022.09.04.506480
DP  - 2022 Jan 01
TA  - bioRxiv
PG  - 2022.09.04.506480
4099  - http://biorxiv.org/content/early/2022/09/05/2022.09.04.506480.short
4100  - http://biorxiv.org/content/early/2022/09/05/2022.09.04.506480.full
AB  - Ras is a central cellular hub protein controlling multiple cell fates. How Ras interacts with a variety of potential effector proteins is relatively unexplored, with only some key effectors characterized in great detail. Here, we have used homology modelling based on X-ray and AlphaFold templates to build structural models for 54 Ras-effectors complexes. These models were used to estimate binding affinities using a supervised learning regressor. Furthermore, we systematically introduced Ras ‘branch-pruning’ (or branchegetic) mutations to identify 200 interface mutations that affect the binding energy with at least one of the model structures. The impacts of these branchegetic mutants were integrated into a mathematical model to assess the potential for rewiring interactions at the Ras hub on a systems level. These findings have provided a quantitative understanding of Ras-effector interfaces and their impact on systems properties of a key cellular hub.Competing Interest StatementThe authors have declared no competing interest.