Zhaleh Bafghi

I am a PhD student of Physics and Chemistry of Biological Systems at SISSA. I received my Master degree from ICTP-Trieste university joint program for higher education in Physics in 2008. The title of my master thesis was "molecular simulation study on the Michaelis complex of human Thymdine kinase1", carried on under the supervision of prof. Paolo Carloni. My BS degree has been completed in Ferdowsi university of Mashhad, Iran in 2006. The Bachelor's project title was "a simulation on granular media" and Dr. Kurosh Javidan was my advisor.





Research project: studies on the permeation of drugs through lipid membrane by atomistic simulations

Oral administration is one of the most important ways of delivering drug. This process is often governed by passive permeation through the cellular membrane (C Acharya et al.,Mol Pharm, 2008). Usually the permeability coefficient (the rate of this permeation) is predicted empirically using QSAR models (G Subramanian et al., J Mol Model, 2006). In my project we study the permeation of drugs through lipid membranes by atomistic simulations. This could be of help in rationalizing the design of the drugs with low permeability coefficient. Particularly, we use an enhanced sampling technique, bias-exchange metadynamics, to explore the free energy landscape of the system using a large number of collective variables. The output is used to construct a kinetic model. This allows obtaining the transition rates between the relevant states and estimating the permeability coefficient. This procedure has been benchmarked for the permeation of ethanol through POPC membrane (see figure). The well-converged free energy profile has been used to calculate the permeability coefficient which is in agreement with the experimental values. We are applying the same procedure to study the permeation process of two anti-HIV drugs.