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     COLLOQUIUM OF THE COMPUTATIONAL MATERIALS SCIENCE CENTER
   AND THE SCHOOL OF PHYSICS, ASTRONOMY AND COMPUTATIONAL SCIENCES
                       (CSI 898-Sec 001)
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        Molecular dynamics simulations of Alzheimer's Abeta peptide 
                   coincubated with ibuprofen
                             Dmitri Klimov
School of Systems Biology, George Mason University, Mannassas, VA

The talk will describe our recent molecular dynamics simulations probing the
impact of common pain-killer drug ibuprofen on Abeta peptides implicated in
Alzheimer’s disease.  We show that ibuprofen binding to Abeta is largely
governed by hydrophobic interactions. Surprisingly, electrostatic interactions
between negatively charged ibuprofen ligands and positively charged side
chains make smaller contribution to binding. This outcome is explained by the
competition of ligand-peptide electrostatic interactions with intrapeptide
salt bridges. Consistent with the experiments the S-isomer of ibuprofen binds
with stronger affinity to Abeta than the R-isomer. Abeta conformational
ensemble is mainly determined by the formation of Asp23-Lys28 salt bridge and
the hydrophobic interactions between the structured regions composed of 19-25
and 29-35 amino acids. Because ibuprofen binding has minor impact on Abeta
structure, we argue that similar peptide structures should be observed in
ligand-free solution.

                      Monday, October 17, 2011
                               4:30 pm
                    Room 301, Research I, Fairfax Campus

Refreshments will be served at 4:15 PM.
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Find the schedule at http://cmasc.gmu.edu/seminar/schedule.html