Engineering of Biological Pathways: Complex Formation and Signal Transduction

Philipp Junk; Christina Kiel

doi:10.1007/978-1-0716-1468-6_4

Engineering of Biological Pathways: Complex Formation and Signal Transduction

Methods Mol Biol. 2021:2315:59-70. doi: 10.1007/978-1-0716-1468-6_4.

Authors

Philipp Junk¹, Christina Kiel²

Affiliations

¹ Systems Biology Ireland and UCD Charles Institute of Dermatology, School of Medicine, University College Dublin, Dublin 4, Ireland.
² Systems Biology Ireland and UCD Charles Institute of Dermatology, School of Medicine, University College Dublin, Dublin 4, Ireland. christina.kiel@ucd.ie.

PMID: 34302670
DOI: 10.1007/978-1-0716-1468-6_4

Abstract

The rational in silico design of interface mutations within protein complexes is a synthetic biology tool that enables-when introduced into biological systems-the artificial rewiring of biological pathways. Here we describe the three-dimensional structure-based design of "rewiring" mutations using the FoldX force field. Specifically, we provide the protocol for the design and selection of interface mutations in three Ras-effector complex structures (PDB entries 3KUD, 4K81, and 6AMB). Ras mutations that impair binding to some but not all interacting partners are selected.

Keywords: Binding energies; FoldX; Interface mutations; Networks; Position energy matrices; Protein engineering.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Computer Simulation
Models, Molecular
Mutation / genetics
Protein Binding / genetics
Protein Engineering / methods
Signal Transduction / genetics*
ras Proteins / genetics

Substances

ras Proteins