Katie Whalen - Hybrid Steered Molecular Dynamics-Docking: An Efficient Solution to the Problem of Ranking Inhibitor Affinities Against a Flexible Drug Target.

Version 1

      Publication Details (including relevant citation   information):

      Mol Inform. 2011 May   16;30(5):459-471.

     
        PMID:  
     
        21738559  
     
        [PubMed]  
     
        PMCID:  
     
        PMC3129543  
     
        [Available on 2012/5/16]  

      Abstract:

      Existing techniques which attempt to predict the affinity of   protein-ligand interactions have demonstrated a direct   relationship between computational cost and prediction accuracy.   We present here the first application of a hybrid ensemble docking and steered molecular dynamics scheme (with a minimized   computational cost), which achieves a binding affinity   rank-ordering of ligands with a Spearman correlation coefficient   of 0.79 and an RMS error of 0.7 kcal/mol. The scheme, termed   Flexible Enzyme Receptor Method by   Steered Molecular Dynamics (FERM-SMD), is applied to   an in-house collection of 17 validated ligands of glutamate   racemase. The resulting improved accuracy in affinity prediction   allows elucidation of the key structural components of a   heretofore unreported glutamate racemase inhibitor (K(i) = 9 µM), a promising new lead   in the development of antibacterial therapeutics.

      Address (URL): http://onlinelibrary.wiley.com/doi/10.1002/minf.201100014/abstract