R. Kiralj, M. M. C. Ferreira, "Molecular Graphics Approach to Bacterial AcrB Protein –  b-Lactam Antibiotic Molecular Recognition in Drug Efflux Mechanism". Rio de Janeiro, RJ, Brazil, 22-25/11/2004: The 2nd Brazilian Symposium on Medicinal Chemistry: Current Trends in Drug Discovery and Development. Abstract Book, (2004) 76. Poster S3-133. Session 3 (S3): Drug Design: Tools in Chemo- and Bioinformatics.

Key words: AcrAB-TolC bacterial efflux pump, b-lactam antibiotics, molecular graphics
Quantum-chemical calculations on 16 b-lactams and four more substrates  (dequalinium, ciprofloxacin, ethidium and rhodamine 6G) of the AcrB component from the AcrAB-TolC bacterial efflux pump have been performed. Molecular graphics methods were used on  the drugs  molecular structures,   available  AcrB  crystal structure  and  the  crystal  structures  of  AcrB  complexes  with  the  four  drugs.
Electronic  features  (dipole moment components and polarizabilities)  as  well as steric properties related to certain principal axes of  the AcrB  substrates showed to be related with stereoelectronic properties of  possible receptors and recognition sites  of  the  AcrB  protein (vestibules, the pore, central cavity receptors)  as well as of the outer leaflet of the inner membrane.  Similarities between the four drugs and the b-lactams enabled,  when combined with the experimental  AcrB - drug  geometry, prediction of b-lactam positions in the AcrB central  cavity.   These  predictions  are  in  reasonable accordance with literature and reveal preferred drug orientation during the efflux process.
 
 

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