Markéta Paloncyova
About me
email: palon@kth.se
My field of focus is mostly in molecular dynamics simulations of biological systems. During my Ph.D. studies I started with drug-membrane interactions and gradually added to the portfolio also membrane enzymes. After my Ph.D. I modeled carbon dots and now at KTH I study fluorescent conjugated probes in bioenvironments.
Drug-Membrane Interactions
Xenobiotics in human bodies interact with variety of lipid membranes. Our body is protected from the outer environment by skin and mostly its outermost layer, stratum corneum (SC), composed of ceramides, free fatty acids, cholesterol and cholesterol sufphate. SC prevents water loss and in respect to fluid cell membranes it is also very impermeable. I studied the drug-membrane interactions with various lipid membrane model by the means of unbiased and biased molecular dynamics simulations and semi-continous tool COSMOmic.
Membrane Enzymes
The xenobiotics on membranes are metabolized by a variety of membrane enzyme and here my focus is on cytochromes P450 (CYPs, cyp.upol.cz/). This family of membrane-embedded enzymes metabolizes most of commonly used drugs. We observed that the composition of lipids in the memrane affects the orientation of CYP and also its internal organisation. Though the secondary structure remains moslty intact, small changes in their mutual positions alter the opening and closing of CYP channels. We also investigated the permeation of a sample drug through CYP3A4 channels by the means of biased-exchange metadynamic simulations and observed that the flexibility of the channels in terms of radii of bottlenecks were the leading factor for free energy barriers for permeation.
Carbon Dots
Carbon dots (CD) are the youngest member of carbon nanomaterial family. These spherical nanoparticles are bioavailable with interesting fluorescence properties, and therefore they are promising in theranostics (therapy + diagnostics) application. In order to investigate their internal structural dynamics, stability and generally to allow molecular dynamics simulations, we prepared a builder plugin for VMD and investigated the role of individual oxygen-containing functional groups on CD surface. We observed rotations of individual CD layers that depended on the layer shape and surface coverage by functional groups.