Journal article
Hybrid Steered Molecular Dynamics-Docking: An Efficient Solution to the Problem of Ranking Inhibitor Affinities Against a Flexible Drug Target
Molecular informatics, Vol.30(5), pp.459-471
05/16/2011
DOI: 10.1002/minf.201100014
PMCID: PMC3129543
PMID: 21738559
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.
Details
- Title: Subtitle
- Hybrid Steered Molecular Dynamics-Docking: An Efficient Solution to the Problem of Ranking Inhibitor Affinities Against a Flexible Drug Target
- Creators
- Katie L. Whalen - University of Illinois Urbana-ChampaignKevin M. Chang - University of Illinois Urbana-ChampaignM. Ashley Spies - University of Illinois Urbana-Champaign
- Resource Type
- Journal article
- Publication Details
- Molecular informatics, Vol.30(5), pp.459-471
- DOI
- 10.1002/minf.201100014
- PMID
- 21738559
- PMCID
- PMC3129543
- ISSN
- 1868-1743
- eISSN
- 1868-1751
- Grant note
- R21 AI076830-01A2 || AI / National Institute of Allergy and Infectious Diseases Extramural Activities : NIAID
- Language
- English
- Date published
- 05/16/2011
- Academic Unit
- Pharmaceutical Sciences and Experimental Therapeutics; Biochemistry and Molecular Biology; Medicinal and Natural Products Chemistry
- Record Identifier
- 9984293080202771
Metrics
8 Record Views