Fig. 3: Difference in binding energy is primarily driven by changes in electrostatic potential in pHLA mediated by the D6 mutation.
From: Therapeutic high affinity T cell receptor targeting a KRASG12D cancer neoantigen
a Enthalpy, entropy, and Gibb’s free energy values obtained from thermodynamic analysis. b–d Color mapping of the differences between JDIa41b1-HLA-A*11-KRASG12D and -HLA-A*11-KRASWT (G12D – WT) in terms of the contribution to the binding energy per residue, showing the residues with higher contribution to the binding energy in G12D (blue) and those with higher contribution in the WT (red). The scale is ±2 kcal.mol-1. The peptide is shown as ball and sticks throughout and any residues with significant differences (P < 0.01) over ±0.25 kcal.mol–1 are shown as sticks. Key residues are labelled. b TCR-pHLA complex with a zoom in on the main changes in the contribution to the binding energy between the WT and G12D peptide bound complexes shown in the box. c pHLA top-down view. d TCR top-down view. e Surface electrostatics of HLA-A*11-KRASWT with the TCR binding zone indicated by dotted white circle. f Surface electrostatics of HLA-A*11-KRASG12D with the TCR binding zone indicated by dotted white circle and key TCR residues in terms of energetic contribution shown as cyan sticks. e, f Surface electrostatics based on static structures prepared for simulation. The scale used is ±2 eV.
