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 obtain hierarchal MD clusters, the biomolecular simulation trajectory and data analysis program cpptraj, 32 which is part of the AMBER package, were used. Clustering is a means of partitioning data so that data points inside a cluster are more similar to each other than they are to points outside a cluster. In the context of molecular simulation, this means grouping similar conformations together. Similarity is determined by a distance metric -the smaller the distance, the more similar the structures. One commonly used distance metric is coordinate root mean square deviation (RMSD). Application of this procedure resulted in four main clusters, from which one centroid conformation PDB structure was chosen for subsequent molecular docking.