Binding energies of tyrosine kinase inhibitors

摘要: Display Omitted Tyrosine kinase inhibitors.Quantum mechanics.Binding energies.Error assessment. The binding energies of imatinib and nilotinib to tyrosine have been determined by quantum mechanical (QM) computations, compared with literature energy studies using molecular mechanics (MM). potential errors in the computational methods include these critical factors:Errors X-ray structures such as structural distortions steric clashes give unrealistically high van der Waals energies, erroneous energies.MM optimization gives a very different configuration QM for nilotinib, whereas ion similar configurationsSolvation are major component overall energy. based solvent model (PCM/SMD) values from those used implicit PBSA MM models. A error inhibitor-kinase lies non-polar solvation terms.Solvent transfer free required empirical accessible surface area factors reverse calculated. These differ studies.An intertwined desolvation-conformational selectivity process is balance thermodynamic desolvation intramolecular conformational kinetic control.The configurational entropies (TΔS) minor sources.