PMID- 18464985
OWN - NLM
STAT- MEDLINE
DCOM- 20080805
LR  - 20131121
IS  - 1463-9076 (Print)
IS  - 1463-9076 (Linking)
VI  - 10
IP  - 19
DP  - 2008 May 21
TI  - A QM/MM study of fluoroaromatic interactions at the binding site of carbonic 
      anhydrase II, using a DFT method corrected for dispersive interactions.
PG  - 2706-14
LID - 10.1039/b715514j [doi]
AB  - The interaction of the fluorinated benzyl ring of a series of inhibitors of 
      carbonic anhydrase II (CAII), fluorine-substituted 
      N-(4-sulfamylbenzoyl)benzylamines (SBB), with nearby residues in the active site 
      has been studied using a hybrid QM/MM model. To account for the important 
      dispersive interactions between the fluorinated benzenes and these residues, a 
      density functional method with an empirical dispersive term, (DFT-D), is used as 
      the QM part of the model. The major interactions are found to be between the 
      substituted benzenes and the aromatic ring of a nearby phenylalanine residue. 
      However, the intermolecular separations between these two groups span a greater 
      range than that found for comparable interactions between isolated molecules, 
      showing the importance of interactions with other residues, which have been 
      quantified. A decomposition of the interaction energy between the fluorobenzenes 
      and each residue has been carried out which shows the dispersive interactions to 
      be dominant. This work has shown that a QM(DFT-D)/MM model is a computationally 
      feasible and accurate way of studying substrate-protein interactions.
FAU - Morgado, Claudio A
AU  - Morgado CA
AD  - School of Chemistry, University of Manchester, Manchester, UK.
FAU - Hillier, Ian H
AU  - Hillier IH
FAU - Burton, Neil A
AU  - Burton NA
FAU - McDouall, Joseph J W
AU  - McDouall JJ
LA  - eng
PT  - Journal Article
DEP - 20080207
PL  - England
TA  - Phys Chem Chem Phys
JT  - Physical chemistry chemical physics : PCCP
JID - 100888160
RN  - 0 (Ligands)
RN  - EC 4.2.1.- (Carbonic Anhydrase II)
RN  - J64922108F (Benzene)
SB  - IM
MH  - Benzene/chemistry
MH  - Binding Sites
MH  - Carbonic Anhydrase II/*chemistry/metabolism
MH  - Cyclization
MH  - Ligands
MH  - Models, Molecular
MH  - *Quantum Theory
EDAT- 2008/05/10 09:00
MHDA- 2008/08/06 09:00
CRDT- 2008/05/10 09:00
PHST- 2008/05/10 09:00 [pubmed]
PHST- 2008/08/06 09:00 [medline]
PHST- 2008/05/10 09:00 [entrez]
AID - 10.1039/b715514j [doi]
PST - ppublish
SO  - Phys Chem Chem Phys. 2008 May 21;10(19):2706-14. doi: 10.1039/b715514j. Epub 2008 
      Feb 7.