QM - Accelrys

QM/MM Application: Cation-Pi Interaction Modeling
• Investigate the binding of Compound 1(active
against Histamine H3 receptor) on AChE 1
• Goal was to design dual-acting compound
• Hypothesis of two cation-pi interactions
between ligand and receptor
• Docking (CDOCKER) of Compound 1 into AChE
receptor (PDB ID 1EVE) yielded a pose in
position to make cation-Pi interactions
• Cation-Pi not modeled well by force fields
• QM/MM geometry optimization suggests
cation-Pi interactions
– 51 hrs on 2 processors
– Multiplicity: Smart
– Quality: Ultra Coarse
– Infinite nonbonded cutoffs
– No constraints/restraints
© 2007 Accelrys, Inc.
Einitial = -15676.278608 kcal/mol
Efinal = -16904.454283 kcal/mol
1. Bembenek, S. D.. et al., Bioorg. Med Chem. (2008),
22