1. Results of numerical simulations, we found that an additional mutation L858R to T790M significantly enhances ATP-binding affinity of the L858R mutant
2. Numerical modeling revealed that the introduction of mutations T790M and L858R / T790M are characterized by a higher affinity for ATPPMP than an increase in the affinity for gefitinib. The increased ATP affinity of the L858R / T790M mutant leads to gefitinib resistance at cellular concentrations of ATP
3. Results of numerical simulations showed the T790M mutation binds gefitinib with a higher affinity than wild-type EGFR.
4. Results of numerical simulations showed the L858R substitution is also characterized by a higher affinity for gefitinib than the wild-type protein.
5. Results of numerical simulations showed substitution G719 has a higher affinity for gefitinib than for wild-type protein.
6. Results of numerical simulations showed substitution of G719S / T790M results in a higher affinity for both gefitinib and AMAPNP.
7. Numerical analysis of the two substitutions G719S and G719S / T790M indicates that the double mutation G719S / T790M results in a greater affinity for gefitinib.
Thus, the numerical method developed by us makes it possible to determine the range of changes in the stability of dimeric complexes with the participation of a small chemical molecule and a protein molecule. Application of our method will allow you to identify mutations that lead to a decrease in the affinity of components. Numerical analysis requires a three-dimensional structure of the dimer under study, in the protein component of which substitutions of amino acid residues will be introduced.