. Author manuscript; available in PMC: 2022 Apr 16.

Published in final edited form as: J Mol Biol. 2021 Feb 1;433(8):166838. doi: 10.1016/j.jmb.2021.166838

Table 2.

GTP-bound KRAS^WT and oncogenic KRAS mutants bind with a similar affinity to the PI3K RBDs, while the T208D mutant in the PI3Kα-RBD does not show detectable binding. All values are for GMPPCP-bound KRAS, except where designated otherwise. Binding stoichiometry (N), K_d, enthalpy (ΔH), and TΔS values were calculated in Origin 7.0 and reported as the mean ± std. dev. as determined by three independent experiments. Gibbs free energy (ΔG) values were calculated using the Gibbs free energy equation and ITC-derived derived ΔH and ΔS values.

RAS protein	Effector	n	K_d (μM)	ΔH (kcal/mol)	TΔS (kcal/mol/deg)	ΔG (kcal/mol
KRAS^WT	PI3Kα-RBD	0.88±0.06	2.2±0.5	−6.12±1.08	1.6±1.3	−7.72
KRAS^WT	PI3Kγ-RBD	0.82±0.08	2.3±0.4	−7.42±0.93	0.30±1.0	−7.72
KRAS^WT-GDP	PI3Kα-RBD	N/A	N/A	N/A	N/A	N/A
KRAS^WT-GDP	PI3Kγ-RBD	N/A	N/A	N/A	N/A	N/A
KRAS^G12V	PI3Kα-RBD	1.07±0.14	2.3±0.5	−3.82±0.37	4.11±0.3	−7.93
KRAS^G12V	PI3Kγ-RBD	0.81±0.16	2.4±0.6	−4.16±0.28	2.96±0.4	−7.12
KRAS^Q61H	PI3Kα-RBD	1.06±0.17	4.0±0.5	− 2.59±0.50	4.7±0.6	−7.29
KRAS^Q61H	PI3Kγ-RBD	0.910±0.01	2.6±1.4	−2.97±0.63	4.7±1.3	−7.67
KRAS^WT	PI3Kα-RBD(T208D)	N/A	N/A	N/A	N/A	N/A