We next examined the conserved water behavior in the simulations by monitoring the water Hbonds and distances to Thr58 and Gly10 (Figure ). The observed H-bond frequencies between side chain oxygen of Thr58 and water, appear to depend on the water model. The TIP4P water model displays much higher frequencies for Thr58-water H-bonds compared to the TIP3P, and this difference occurs with higher magnitude with the compounds that possess the highest WaterMap predicted energies (sotorasib, AZD4625, JDQ443 and MRTX1133). The discrepancy between the water models in Gly10(NH)-water H-bonds is less profound. The lowest frequencies of Gly10(NH)-water H-bonds are observed for AZD4625 and MRTX1133, while "compound 5B" and G12Si-1 exhibit the highest frequencies. The water presence near Thr58 oxygen is the lowest with AZD4625 and JDQ443 based on the minimum water distance (Figure ), while AZD4625 also appears to push the water away from Gly10 nitrogen (Figure ). Generally, we observed lower distances between water and the investigated protein atom(s) with TIP4P water model compared to TIP3P (Figure ).