IN THIS PROJECT, WE STUDIED SOME COMPUTER SIMULATIONS ON TWO TYPES OF ANTICANCER DRUGS, FLAVONOL (QUERCETIN) AND FLAVONES (APIGENIN) IN A LIPID BILAYER. IN THIS WORK THE EFFECTS OF DRUGS ON A LIPID BILAYER MEMBRANE PROPERTIES SUCH AS ELECTROSTATIC POTENTIAL, ORDER PARAMETER, DIFFUSION COEFFICIENTS, HYDROGEN BOND FORMATION, RADIAL DISTRIBUTION FUNCTION(RDF) AND MASS DENSITY ANALYSES WERE INVESTIGATED WITH USING GROMACS SOFTWARE. AFTER ENERGY MINIMIZATION THE EQUILIBRIUM STEP (NVT AND NPT) WAS PERFORMED AND THE LAST MOLECULAR DYNAMICS SIMULATION WAS DONE. DIPALMITOYL PHOS PHATIDYL CHOLINE (DPPC) AND WATER WAS USED AS REFERENCE SYSTEM AND THE OTHER SYSTEMS WERE COMPARED WITH REFERENCE SYSTEM. RESULTS SHOWED THAT HYDROGEN BONDING ENERGY BETWEEN QUERCETIN WITH DPP AND WATER IS HIGHER THAN HYDROGEN BONDING BETWEEN APIGENIN WITH DPPC AND WATER CONSEQUENTLY. SO DIFFUSION COEFFICIENT OF QUERCETIN WILL BE LESS THAN APIGENIN. ORDER PARAMETER FOR DPPC CHAINS WAS DONE. RDF ANALYSIS SHOWED THE NUMBER OF WATERS AROUND DRUG MOLECULES. MASS DENSITY OF WATER, DRUGS AND MEMBRANE WAS INVESTIGATED.

Introduction: Ion channels in mitochondria and RER have important roles in intracellular signaling. Recent studies demonstrate that mitochondrial potassium channels participate in cell death and apoptosis, but there isn't any information about pharmacological and electrophysiological characteristics of RER potassium channel. Our former studies demonstrated low opening frequency of RER potassium channel in voltage less than 30 mV. Therefore, it is important to find physiological factors to increase channel open probability. The channel phosphorylation is one of the most important factors to control channel gating, thus purpose of this study is to consider effect of ADP-Mg on channel behavior.Methods: We used single channel recording method after incorporation of microsomes into phosphatydilcholine bilayer lipid membrane. Subsequently, PC extraction by singleton protocol, BLM making in 250 µM holes by Muller technique and RER extraction through Can method were carried out. After incorporation of protein channel in BLM, channel activity was recorded and data have been interpreted using Noise Free Markov's analysis and clampfit9 software.Results: our results showed that ADP-Mg 2.5 mM didn't affect RER potassium channel activities at voltage of +40mV. While, adding ADP-Mg in cytoplasmic face increased significantly mean open probability (Po) from 0.02 to 0.7 at different voltages (-10, 0, and +20 mV) less than reverse potential (+30 mV).Discussion: This study demonstrates ADP-Mg increased RER potassium channel activity as voltage dependent manner. Channel phosphorylation induced very high Po at low voltages near ER physiological resting membrane potential. It seems this channel will be more activated by phosphorylation and controls by metabolic variables and probably involved in ER lumen homeostasis and cell protection.

Introduction: Our study confirms presence of potassium channel in RER membrane; but its pharmacological characteristics were unknown. The inhibitory effect of ATP on mitochondrial potassium channel has been documented. Distinguishing Nucleotides effect on RER potassium channel is important due to physiological significance and its role in disease pathogenesis and cell protection. Methods: We used single channel recording method after incorporation of microsomes into phosphatydilcholine (PC) bilayer. Subsequently, PC extraction by singleton protocol, BLM making in 250 µM holes by Muller technique and RER extraction through Can method were carried out. Channel activity was recorded and data have been interpreted using Noise Free Markov's analysis and clampfit9 software. Results: Results represent ATP in 2.5, 1.25 and 0.25 mM in cytoplasmic face and in +40 mV caused inhibitory effect on potassium channel activity; But 100 µM ATP reduced channel open probability from 0.7 to 0.3 .this effect couldn't have seen at 0 mV. In spite of blocking effect of ATP, There wasn't observed any effect by 2.5 mM ADP. Discussion: Intracellular channels are involved in regulation of cellular function and apoptosis. Studying pharmacological characteristics in this research represents blocking effect of ATP on channel but ADP didn't have this effect. Therefore, ATP will block RER potassium channel activities in a dose-and voltage-dependent manners. Studies demonstrate ATP sensitive potassium channels have been blocked by ATP and ADP but our study represent RER potassium channel have different pharmacological behavior. Results shows presence of an ATP sensitive potassium channel in RER which probably involves in metabolic regulation and its gating is control by metabolic factors.

Many types of Cl- channels have been reported in cell membranes and various types of intracellular organelles including endoplasmic reticulum (ER). Although the exact role of these channels is not clear, it has been suggested that it might contribute to counter currents during Ca2+ release and uptake and regulate transmembrane ion fluxes. Studies designed to determine functional characteristics of channels can help understand their performance and expand perception of cell physiology. The ER was extracted from rat liver by homogenization and ultra centrifugation for several times. Bilayer lipid membrane (BLM) was formed using phosphatidyl choline on 250 μm diameter aperture in between Cis and Trans chambers containing KCL 200 and 50 mM respectively. ER vesicles were incorporated into BLM and then Cl- channel activity was studied using single channel recording technique. The studied Cl- channel current amplitude was equivalent to 6 pA. The conductance was about 105 picosiemens and thecurrentvoltage relationship curve was also linear. The channel had a voltage-independent behavior and its open probability (Po) was low being around 0.07. Channel activity was inhibited by DIDS with a concentration of 0.1 mM. Because the channel open probability was low in different voltages and was not affected by voltage changes, the studied channel is probably a non-voltage-dependent channel and gating kinetic behavior is controlled by ligands.