An evaluation of MM/PB(GB)SA methods applied to kinase systems, assigning differents interior dielectric constant (ε=1,2,4), using MD simulations and taking the top-score docking poses for rescoring, is presented. They exhibited that higher ε values are preferred to consider the electronic polarization effect. Speaking of taking docking poses, the influence of the use of multiple docking poses for rescoring is not significant and can be avoided if the rescoring function offers good ranking. Also, for these particular systems, MD simulations does not improve considerably enrichment (criterion to evaluate whether a theoretical model can discriminate known inhibitors from non-inhibitors), however as optimization tool can be very helpful for MM/PB(GB)SA rescoring.
An evaluation of MM/PB(GB)SA methods applied to kinase systems, assigning differents interior dielectric constant (ε=1,2,4), using MD simulations and taking the top-score docking poses for rescoring, is presented. They exhibited that higher ε values are preferred to consider the electronic polarization effect. Speaking of taking docking poses, the influence of the use of multiple docking poses for rescoring is not significant and can be avoided if the rescoring function offers good ranking. Also, for these particular systems, MD simulations does not improve considerably enrichment (criterion to evaluate whether a theoretical model can discriminate known inhibitors from non-inhibitors), however as optimization tool can be very helpful for MM/PB(GB)SA rescoring.