Virtual screening for potential inhibitors of Mcl-1 conformations sampled by normal modes, molecular dynamics, and nuclear magnetic resonance

Glantz-Gashai, Yitav; Meirson, Tomer; Reuveni, Eli; Samson, Abraham O

To calculate normal modes of the Mcl-1 structure PDB ID 2MHS, 28 model 1, two programs were utilized, namely, STAND 23 and ElNémo. 29 For STAND, both real normal modes (REA) and Tirion modes (TIR) were calculated. For speed, the STAND option of coarse graining, 1 point, which accelerates the calculations yet does not flaw the results, was used, and default values of deformation amplitude were used. For ElNémo, default values of DQMIN -100 and DQMAX 100 were utilized. The DQMIN and DQMAX parameters correspond to the deformation amplitude in the direction of a single normal mode. For both STAND and ElNémo, only the three non-trivial lowest frequency modes were calculated. For each of these three modes, six PDB models were generated by STAND and six model structures were generated by ElNémo all fully distorted along the particular mode. These 12 model structures were subsequently used for molecular docking.