Modelling of the mutant codon 19 phenylalanine and codon 20 alanine side chains into the K-RAS protein. (A) The GDP/GTP binding pocket of wildtype K-RAS. The white residues are codons 19 and 20. The loop on the left of the helix forms the GDP/GTP binding pocket of K-RAS. Residues coloured blue represent the mutational hotspot codons 12 and 13. The shortened K-RAS protein structure used for modelling was obtained from the Protein Data Bank (PDB ID:3gft) and visualised using PyMOL (http://www.pymol.org webcite). (B) The GDP/GTP binding pocket of wildtype K-RAS with wildtype side chains of codons 19 and 20 and a non-hydrolysable GTP analogue (used during crystallisation) adjacent to codons 12 and 13. (C and D) Modelling of the mutant phenylalanine (codon 19) and alanine (codon 20) side chains into the K-RAS protein, predicts projection of the bulky phenylalanine side chain into the main body of the protein and replacement of the OH containing side chain of threonine with the small aliphatic side chain of alanine. The mutant side chains were modelled into positions of the protein which produced the fewest conflicting Van der Waals radii and the configuration with the least steric interference with other amino acid side chains.
Naguib et al. Journal of Molecular Signaling 2011 6:2 doi:10.1186/1750-2187-6-2