The influence of cholesterol on interactions and dynamics of ibuprofen in a lipid bilayer.

In this work, molecular dynamics (MD) simulations with atomistic details were performed to examine the influence of the cholesterol on the interactions and the partitioning of the hydrophobic drug ibuprofen in a fully hydrated 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) bilayer. Analysis of MD simulations indicated that ibuprofen molecules prefer to be located in the hydrophobic acyl chain region of DMPC/cholesterol bilayers. This distribution decreases the lateral motion of lipid molecules. The presence of ibuprofen molecules in the bilayers with 0 and 25mol% cholesterol increases the ordering of hydrocarbon tails of lipids whereas for the bilayers with 50mol% cholesterol, ibuprofen molecules perturb the flexible chains of DMPC lipids which leads to the reduction of the acyl chain order parameter. The potential of the mean force (PMF) method was used to calculate the free energy profile for the transferring of an ibuprofen molecule from the bulk water into the DMPC/cholesterol membranes. The PMF studies indicated that the presence of 50mol% cholesterol in the bilayers increases the free energy barrier and slows down the permeation of the ibuprofen drug across the DMPC bilayer. This can be due to the condensing and ordering effects of the cholesterol on the bilayer.

Effect of cholesterol on behavior of 5-fluorouracil (5-FU) in a DMPC lipid bilayer, a molecular dynamics study.

In this work, molecular dynamics (MD) simulations were performed to investigate the effects of cholesterol on the interaction between the hydrophilic anticancer drug, 5-FU, and fully hydrated 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) bilayer. Several structural and dynamical parameters of DMPC bilayers with varying amounts of cholesterol (0, 25, and 50mol%) in the presence and absence of drug molecules were calculated. Moreover, the free energy barriers for translocation of one 5-FU molecule from water to the lipid bilayer were determined by using the potential of mean force (PMF). PMF studies indicated that the location of the maximum free energy barrier was in the hydrophobic middle region of bilayer, while the minimums of the barrier were located at the hydrophilic part of bilayer at the interface with water. The minimum and maximum of the free energy profiles were independent of cholesterol concentration and suggested that the drug molecules 5-FU were accumulated in the vicinity of the polar head group of lipid bilayers. Moreover, the results showed that with increasing cholesterol concentration in the bilayer, the free energy barrier for translocation of 5-FU across the bilayer also increases which can be attributed to the condensing effect of the cholesterol on the bilayer.

QSPR prediction of flash point of esters by means of GFA and ANFIS.

A quantitative structure property relationship (QSPR) study was performed to develop a model for prediction of flash point of esters based on a diverse set of 95 components. The most five important descriptors were selected from a set of 1124 descriptors to build the QSPR model by means of a genetic function approximation (GFA). For considering the nonlinear behavior of these molecular descriptors, adaptive neuro-fuzzy inference system (ANFIS) method was used. The ANFIS and GFA squared correlation coefficient for testing set was 0.969 and 0.965, respectively. The results obtained showed the ability of developed GFA and ANFIS for prediction of flash point of esters.