Modeling Enantiomeric Separations as an Interfacial Process Using Amylose Tris(3,5-dimethylphenyl carbamate) (ADMPC) Polymers Coated on Amorphous Silica.

Chiral high-performance liquid chromatography (HPLC) is commonly performed to isolate the biologically active enantiomer of a drug from the ineffective or even harmful ones. Understanding the molecular-level recognition that underlies this process is necessary for trimming down the very large number of possible combinations of chiral stationary phases, solvent systems, and other experimental HPLC conditions, a particularly important consideration when only small quantities of the racemate are available. Fully atomistic molecular dynamics (MD) simulation is a useful tool to provide this molecular-level understanding and predict experimental separation factors under a given set of conditions. To predict the chiral separation results for drug enantiomers by amylose tris(3,5-dimethylphenyl carbamate) (ADMPC) chiral stationary phase, we design a model of multiple ADMPC polymer strands coated on an amorphous silica slab. Using various MD techniques, we successfully coat ADMPCs onto the surface without losing the structural character of the backbone in the presence of the solvent system. Not only is this model more representative of the polymer surface on a solid support that is encountered by the enantiomers, but it also provides more opportunities for chiral molecules interacting with ADMPC, provides the possibility for large drug molecules to interact with two polymer strands at the same instant, and provides better agreement with experiment when we use the overall average quantities as the predictive metric. For a better understanding of why some metrics are better predictors than others, we use charts of the distribution of hydrogen-bonding lifetimes for various donor-acceptor pairs that contribute to the interaction events determining the relative retention times for the enantiomers. We also examine the contribution of ring-ring interactions to the molecular recognition process and ultimately to the differential retention of enantiomers. The results are more consistent than previous models and resolve the problematic case of two drugs, thalidomide and valsartan.

Atomistic Simulations of Biofouling and Molecular Transfer of a Cross-linked Aromatic Polyamide Membrane for Desalination.

Reverse osmosis through a polyamide (PA) membrane is an important technique for water desalination and purification. In this study, molecular dynamics simulations were performed to study the biofouling mechanism (i.e., protein adsorption) and nonequilibrium steady-state water transfer of a cross-linked PA membrane. Our results demonstrated that the PA membrane surface's roughness is a key factor of surface's biofouling, as the lysozyme protein adsorbed on the surface's cavity site displays extremely low surface diffusivity, blocking water passage, and decreasing water flux. The adsorbed protein undergoes secondary structural changes, particularly in the pressure-driven flowing conditions, leading to strong protein-surface interactions. Our simulations were able to present water permeation close to the experimental conditions with a pressure difference as low as 5 MPa, while all the electrolytes, which are tightly surrounded by hydration water, were effectively rejected at the membrane surfaces. The analysis of the self-intermediate scattering function demonstrates that the dynamics of water molecules coordinated with hydrogen bonds is faster inside the pores than during the translation across the pores. The pressure difference applied shows a negligible effect on the water structure and content inside the membrane but facilitates the transportation of hydrogen-bonded water molecules through the membrane's sub-nanopores with a reduced coordination number. The linear relationship between the water flux and the pressure difference demonstrates the applicability of continuum hydrodynamic principles and thus the stability of the membrane structure.

Xenon Recovery by DD3R Zeolite Membranes: Application in Anaesthetics.

Xe is only produced by cryogenic distillation of air, and its availability is limited by the extremely low abundance. Therefore, Xe recovery after usage is the only way to guarantee sufficient supply and broad application. Herein we demonstrate DD3R zeolite as a benchmark membrane material for CO2 /Xe separation. The CO2 permeance after an optimized membrane synthesis is one order magnitude higher than for conventional membranes and is less susceptible to water vapour. The overall membrane performance is dominated by diffusivity selectivity of CO2 over Xe in DD3R zeolite membranes, whereby rigidity of the zeolite structure plays a key role. For relevant anaesthetic composition (<5 % CO2 ) and condition (humid), CO2 permeance and CO2 /Xe selectivity stabilized at 2.0×10-8  mol m-2 s-1 Pa-1 and 67, respectively, during long-term operation (>320 h). This endows DD3R zeolite membranes great potential for on-stream CO2 removal from the Xe-based closed-circuit anesthesia system. The large cost reduction of up to 4 orders of magnitude by membrane Xe-recycling (>99+%) allows the use of the precious Xe as anaesthetics gas a viable general option in surgery.

The Composition of the Mobile Phase Affects the Dynamic Chiral Recognition of Drug Molecules by the Chiral Stationary Phase.

More than half of all pharmaceuticals are chiral compounds. Although the enantiomers of chiral compounds have the same chemical structure, they can exhibit marked differences in physiological activity; therefore, it is important to remove the undesirable enantiomer. Chromatographic separation of chiral enantiomers is one of the best available methods to get enantio-pure substances, but the optimization of the experimental conditions can be very time-consuming. One of the most widely used chiral stationary phases, amylose tris(3,5-dimethylphenyl carbamate) (ADMPC), has been extensively investigated using both experimental and computational methods; however, the dynamic nature of the interaction between enantiomers and ADMPC, as well as the solvent effects on the ADMPC-enantiomer interaction, are currently absent from models of the chiral recognition mechanism. Here we use QM/MM and molecular dynamics (MD) simulations to model the enantiomers of flavanone on ADMPC in either methanol or heptane/2-propanol (IPA) (90/10) to elucidate the chiral recognition mechanism from a new dynamic perspective. In atomistic MD simulations, the 12-mer model of ADMPC is found to hold the 4/3 left-handed helical structure in both methanol and heptane/IPA (90/10); however, the ADMPC polymer is found to have a more extended average structure in heptane/IPA (90/10) than in methanol. This results from the differences in the distribution of solvent molecules close to the backbone of ADMPC leads to changes in the distribution of the (φ, ψ) dihedral angles of the glycoside bond (between adjacent monomers) that define the structure of the polymer. Our simulations have shown that the lifetime of hydrogen bonds formed between ADMPC and flavanone enantiomers in the MD simulations are able to reproduce the elution order observed in experiments for both the methanol and the heptane/IPA solvent systems. Furthermore, the ratios of hydrogen-bonding-lifetime-related properties also capture the solvent effects, in that heptane/IPA (90/10) is found to make the separation between the two enantiomers of flavanone less effective than methanol, which agrees with the experimental separation factors of 0.9 versus 0.4 for R/S, respectively.

Simulated Permeation and Characterization of PEGylated Gold Nanoparticles in a Lipid Bilayer System.

PEGylated gold nanoparticles are considered suitable nanocarriers for use in biomedical applications and targeted drug delivery systems. In our previous investigation with the alkanethiol-functionalized gold nanoparticle, we found that permeation across a protein-free phospholipid membrane resulted in damaging effects of lipid displacement and water and ion leakage. In the present study, we carry out a series of coarse-grained molecular simulations to explore permeation of lipid bilayer systems by a PEGylated gold nanoparticle, especially at the bulk-liquid-lipid interface as well as the interface between the two lipid leaflets. Initially, we examine molecular-level details of a PEGylated gold nanoparticle (constructed from cycled annealing) in water and find a distribution of ligand configurations (from mushroom to brush states) present in nanoparticles with medium to high surface coverage. We also find that the characteristic properties of the PEGylated gold nanoparticle do not change when it is placed in a salt solution. In our permeation studies, we investigate events of water and ion penetration as well as lipid translocation while varying the ligand length, nanoparticle surface coverage, and ion concentration gradient of our system. Results from our studies show the following: (1) The number of water molecules in the interior of the membrane during ligand-coated nanoparticle permeation increases with PEGn-SH surface coverage, ligand length, and permeation velocity but is not sensitive to the ion concentration gradient. (2) Lipid molecules do not leave the membrane; instead they complete trans-bilayer lipid flip-flop with longer ligands and higher surface coverages. (3) The lack of formation of stable water pores prevents ion translocation. (4) The PEGylated nanoparticle causes less damage to the membrane overall due to favorable interactions with the lipid headgroups which may explain why experimentalists observe endocytosis of PEGylated nanocarriers in vivo.

Surface-functionalized nanoparticle permeation triggers lipid displacement and water and ion leakage.

Functionalized nanoparticles (NPs) are considered suitable carriers for targeted drug delivery systems. However, the ion and water leakage induced by permeation of these nanoparticles is a challenge in these drug delivery methods because of cytotoxic effects of some ions. In this study, we have carried out a series of coarse-grained molecular dynamics simulations to investigate the effect of length of ligands on permeation of a nanoparticle across a protein-free phospholipid bilayer membrane. Water and ion penetration as well as incidence of lipid flip-flop events and loss of lipid molecules from the membrane are explored in this study while varying the nanoparticle size, length of ligand, ion concentration gradient, pressure differential across the membrane, and nanoparticle permeation velocity. Some results from our studies include (1) the number of water molecules in the interior of the membrane during ligand-coated nanoparticle permeation increases with nanoparticle size, ligand length, pressure differential, and permeation velocity but is not sensitive to the ion concentration gradient; (2) some lipid molecules leave the membrane by being entangled with ligands of the NP instead of completing the flip-flop that permits them to rejoin the membrane, thereby leading to fewer flip-flop events; and (3) the formation of water columns or water "fingers" provides a mechanism of ion transport across lipid bilayer membranes, but such ion penetration events are less likely for sodium ions than chloride ions and less likely for nanoparticles with longer-ligands.

Communication: A tractable design for a thermal transistor.

We propose a conceptual design for a logic device that is the thermal analog of a transistor. It has fixed hot (emitter) and cold (collector) temperatures, and a gate controls the heat current. Thermal logic could be applied for thermal digital computing, enhance energy conservation, facilitate thermal rheostats, and enable the transport of phononic data. We demonstrate such a device using molecular dynamics simulations that consider thermal transport across hot and cold solid Si regions that seal water within them. Changes in the hot side, or emitter, heat current are linear with respect to varying gate temperature but the corresponding variation in the collector current is nonlinear. This nonlinear variation in collector current defines the ON and OFF states of the device. In its OFF state, the thermal conductivity of the device is positive. In the ON state, however, more heat is extracted through the cold terminal than is provided at the hot terminal due to the intervention of the base terminal. This makes it possible to alter the transport factor by varying the gate conditions. When the device is ON, the transport factor is greater than unity, i.e., more heat is rejected at the collector than is supplied to the emitter.

Preparation of (99m)Tc-labelled methotraxate by a direct labeling technique as a potential diagnostic agent for breast cancer and preliminary clinical results.

Methotrexate (MTX) is being used in clinical oncology for the treatment of a wide variety of cancers. The aim of the present study was to label directly MTX with (99m)Tc by using Sn/pyrophosphate as reducing agent and to use this labeled compound as a potential anticancer radiopharmaceutical for breast cancer imaging. We studied the labeling efficiency of the (99m)Tc-MTX compound by paper chromatography and instant thin layer chromatography (ITLC) in acetone and saline and found it to be more than 95%. In vitro stability of labeled MTX in serum was studied up to 5h. Partition coefficient in n-octanol and saline indicated that the labeled radiopharmaceutical was hydrophilic. We then tested (99m)Tc-MTX in 5 breast cancer female patients. Protein bound (99m)Tc-MTX showed rapid clearance from blood. The biodistibution data suggested that (99m)Tc-MTX was cleared by the kidneys and the liver. Patients ' data also showed highly significant uptake of (99m)Tc-MTX in breast cancer. In conclusion, this study indicated that (99m)Tc-MTX may be used as a potential diagnostic agent for breast cancer patients imaging and may show treatment efficiency in case MTX is to be used for treatment.

Development of 99mTc-5-fluorouracil as a potential tumor diagnostic agent.

5-Fluorouracil is a well know drug for chemotherapy of various types of cancer. In the present study, we radiolabeled 5-fluorouracil with (99m)Tc for a diagnostic study of cancer. After successful labeling of the drug we performed an animal study to evaluate the potential of this radiopharmaceutical as a tumor diagnostic agent. The results showed 98.1 ± 1.2% labeling efficacy of 5-fluorouracil with (99m)Tc. The in vitro stability of the radiolabeled drug at room temperature at 4 hr of post-labeling was >96.5 ± 0.4%. The binding of the radiolabeled drug with plasma proteins was 66.6 ± 3%. Partition coefficient results showed that this drug is hydrophilic in nature. Biodistribution study in rabbit models displayed faint uptake in liver. Both kidney and bladder were prominent as excretory route of the labeled drug. Bioevaluation was performed in Swiss Webster mice having naturally developed tumor. Mice were dissected, uptake of drug in various organs was studied and results showed prominent uptake in liver and tumor. Tumor was further investigated by histopathological study.

In house development of (99m)Tc-Rhenium sulfide colloidal nanoparticles for sentinel lymph node detection.

In this study, rhenium sulfide colloidal nanoparticles were developed as radiopharmaceutical for sentinel lymph node detection. We directly used rhenium sulfide as a starting material for the preparation of colloidal nanoparticles. UV-visible spectrophotometry was used for characterization of in house developed colloidal particles. The size distribution of radioactive particles was studied by using membrane filtration method. The percentage of radiolabeled colloidal nanoparticles was determined by paper chromatography (PC). The study also includes in vitro stability, protein binding in human blood and bioevaluation in a rabbit model. The results indicate that 77.27 ± 3.26 % particles of size less than 20nm (suitable for lymphoscintigraphy) were radiolabeled. (99m)Tc labeled rhenium sulfide labeling efficacy with the radiometal is 98.5 ± 0.5%, which remains considerably stable beyond 5h at room temperature. Furthermore, it was observed that 70.2 ± 1.3% radiolabeled colloid complex showed binding with the blood protein. Bioevaluation results show the remarkable achievement of our radiopharmaceutical. The in house prepared (99m)Tc labeled rhenium sulfide colloidal nanoparticles reached the sentinel node within 15 min of post injection. These results indicate that (99m)Tc labeled rhenium sulfide colloid nanoparticles kit produced by a novel procedure seems of significant potential as a feasible candidate for further development to be used in clinical practice.

Synthesis, characterization and bioevaluation of technetium-99m labeled N-(2-Hydroxybenzyl)-2-amino-2-deoxy-D-glucose as a tumor imaging agent.

N-(2-Hydroxybenzyl)-2-amino-2-deoxy-D-glucose (NHADG) was synthesized by conjugation of salicylaldehyde to glucosamine. The obtained compound was well characterized via different analytical techniques. Labeling of the synthesized compound with technetium-99m ((99m)Tc) in pertechnetate form ((99m)Tc O4-) was carried out via chelation reaction in the presence of stannous chloride dihydrate. Maximum radiochemical yield of (99m)Tc-NHADG complex (99%) was obtained by using 1 mg NHADG, 200 µg SnCl2.2H2O, at pH 9.5 and reaction time of 15 min. The radiochemical purity of the (99m)Tc-NHADG complex was measured by instant thin layer chromatography (ITLC) and paper chromatography (PC), without any notable decomposition at room temperature over a period of 4h. The biological evaluation results show that the (99m)Tc labeled NHADG conjugate is able to specifically target mammary carcinoma in mice models, thus highlighting its potential as an effective (99m)Tc labeled glucose-derived agent for tumor imaging.

Xe Recovery from Nuclear Power Plants Off-Gas Streams: Molecular Simulations of Gas Permeation through DD3R Zeolite Membrane.

Recent experimental work has shown zeolite membrane-based separation as a promising potential technology for Kr/Xe gas mixtures due to its much lower energy requirements in comparison to cryogenic distillation, the conventional separation method for such mixtures. Such a separation is also economically rewarding because Xe is in high demand, as a valuable product for many applications/processes. In this work, we have used Molecular Dynamics (MD) simulations to study the effects of different conditions, i.e., temperature, pressure, and gas feed composition, on Kr/Xe separation performance via DD3R zeolite membranes. We provide a comprehensive study of the permeation of the different gas species, density profiles, and diffusion coefficients. Molecular simulations show that if the feed is changed from pure Kr/Xe to an equimolar mixture, the Kr/Xe separation factor increases, which agrees with experiments. In addition, when Ar is introduced as a sweep gas, the adsorption of both Kr and Xe increases, while the permeation of pure Kr increases. A similar behavior is observed with equimolar mixtures of Kr/Xe with Ar as the sweep gas. High-separation Kr/Xe selectivity is observed at 50 atm and 425 K but with low total permeation rates. Changing pressure and temperature are found to have profound effects on optimizing the separation selectivity and the permeation throughput.

Nanoparticle permeation induces water penetration, ion transport, and lipid flip-flop.

Nanoparticles are generally considered excellent candidates for targeted drug delivery. However, ion leakage and cytotoxicity induced by nanoparticle permeation is a potential problem in such drug delivery schemes because of the toxic effect of many ions. In this study, we have carried out a series of coarse-grained molecular dynamics simulations to investigate the water penetration, ion transport, and lipid molecule flip-flop in a protein-free phospholipid bilayer membrane during nanoparticle permeation. The effect of ion concentration gradient, pressure differential across the membrane, nanoparticle size, and permeation velocity have been examined in this work. Some conclusions from our studies include (1) The number of water molecules in the interior of the membrane during the nanoparticle permeation increases with the nanoparticle size and the pressure differential across the membrane but is unaffected by the nanoparticle permeation velocity or the ion concentration gradient. (2) Ion transport is sensitive to the size of nanoparticle as well as the ion concentration gradient between two sides of the membrane; no anion/cation selectivity is observed for small nanoparticle permeation, while anions are preferentially translocated through the membrane when the size of nanoparticle is large enough. (3) Incidences of lipid molecule flip-flop increases with the size of nanoparticle and ion concentration gradient and decreases with the pressure differential and the nanoparticle permeation velocity.

Note: the role of external electric fields in enhancing ion mobility, drift velocity, and drift-diffusion rates in aqueous electrolyte solutions [J. Chem. Phys. 134, 114504 (2011)].

The effect of external electric fields on enhancing ion mobility, drift velocity, and drift diffusion as a function of solution concentration has been investigated using molecular dynamics simulations. Our results show that the unusual nonlinear behavior observed when the solution concentration matches seawater is also observed when the concentration is reduced to half of that value. These results are of significance in designing processes for desalinating seawater using electro-deionization in which the concentration would decrease during salt removal, and for purification of brackish waters which also have lower salt content.

Communication: Thermal rectification in liquids by manipulating the solid-liquid interface.

Thermal rectification, the origin of which lies in modifying the thermal resistance in a nonlinear manner, could significantly improve the thermal management of a wide range of nano-devices (both electronic and thermoelectric), thereby improving their efficiencies. Since rectification requires a material to be inhomogeneous, it has been typically associated with solids. However, the structure of solids is relatively difficult to manipulate, which makes the tuning of thermal rectification devices challenging. Since liquids are more amenable to tuning, this could open up new applications for thermal rectification. We use molecular dynamics simulations to demonstrate thermal rectification using liquid water. This is accomplished by creating an inhomogeneous water phase, either by changing the morphology of the surface in contact with the liquid or by imposing an arbitrary external force, which in practice could be through an electric or magnetic field. Our system consists of a bulk fluid that is confined in a reservoir that is bounded by two walls, one hot and the other cold. The interfacial (Kapitza) thermal resistance at the solid-fluid interface and the density gradient of the bulk fluid both influence the magnitude of the thermal rectification. However, we find that the role of the interfacial resistance is more prominent than the application of an external force on the bulk fluid.

Novel methods to characterise spatial distribution and enantiomeric composition of usnic acids in four Icelandic lichens.

Usnic acid is an antibiotic metabolite produced by a wide variety of lichenized fungal lineages. The enantiomers of usnic acid have been shown to display contrasting bioactivities, and hence it is important to determine their spatial distribution, amounts and enantiomeric ratios in lichens to understand their roles in nature and grasp their pharmaceutical potential. The overall aim of the study was to characterise the spatial distribution of the predominant usnic acid enantiomer in lichens by combining spatial imaging and chiral chromatography. Specifically, separation and quantification of usnic acid enantiomers in four common lichens in Iceland was performed using a validated chiral chromatographic method. Molecular dynamics simulation was carried out to rationalize the chiral separation mechanism. Spatial distribution of usnic acid in the lichen thallus cross-sections were analysed using Desorption Electrospray Ionization-Imaging Mass Spectrometry (DESI-IMS) and fluorescence microscopy. DESI-IMS confirmed usnic acid as a cortical compound, and revealed that usnic acid can be more concentrated around the algal vicinity. Fluorescence microscopy complemented DESI-IMS by providing more detailed distribution information. By combining results from spatial imaging and chiral separation, we were able to visualize the distribution of the predominant usnic acid enantiomer in lichen cross-sections: (+)-usnic acid in Cladonia arbuscula and Ramalina siliquosa, and (-)-usnic acid in Alectoria ochroleuca and Flavocetraria nivalis. This study provides an analytical foundation for future environmental and functional studies of usnic acid enantiomers in lichens.

The role of external electric fields in enhancing ion mobility, drift velocity, and drift-diffusion rates in aqueous electrolyte solutions.

Molecular simulations have been carried out using the method of molecular dynamics to investigate the role of external electric fields on the ion mobility, drift velocity, and drift-diffusion rate of ions in aqueous electrolyte solutions. These properties are critical for a range of processes including electrodialysis, electro-deionization, electrophoresis, and electroosmosis. Our results show that external electric fields relax the hydrated ion structure at significantly larger time scales (between 300 and 800 ps), than most other relaxation processes in solutions (generally of the order of 1 ps). Previous studies that did not account for the much longer relaxation times did not observe this behavior for ions even with very high electric fields. External electric fields must also overcome several (at least two or more) activation energy barriers to significantly change the structure of hydrated ions. As a result, the dynamic behavior changes almost in bands as a function of electric field strengths, rather than linearly. Finally, the effect of the field is much less dramatic on water than the ions. Thus electric fields will be of more significance in processes that involve the transport of ions (such as electro-deionization) than the transport of water (electroosmosis).

How the capillarity and ink-air flow govern the performance of a fountain pen.

As kids, the authors enjoyed learning how to write by dipping nib pens into ink, and then later, using flex nib pens for calligraphy. They remember, less fondly, the troubles with ink leaks and spills over the paper's surface. Despite advances in fountain pen design, the performance of fountain pens is still not perfect. A robust fountain pen has to provide a sustainable ink flow-no leaks-for smooth and precise writing on paper. In the long history of the design and development of fountain pens, more attention has been focused on the ink flow than on the ink/air capillary flow balance. It is found that as ink flows out of the cartridge, the holding pressure in the ink cartridge builds up and the pressure drop across the capillary valve increases. Consequently, the air is sucked toward the ink cartridge. An air-ink meniscus is formed at the capillary valve and finally breaks into air bubbles due to Rayleigh instability. The air bubbles float into the ink cartridge under buoyancy force to reduce the holding pressure so that the ink can continuous flow out to the nib to keep the fountain pen in function. The unbalance between the air holding pressure in the ink cartridge and the pressure drop across the capillary valve is the key for the functionality of the fountain pen. A poor design of the feed/cartridge connection with a small orifice of the capillary valve leads to the malfunction of the fountain pen.

Post mastectomy adjuvant radiotherapy in breast cancer: a comparision of three hypofractionated protocols.

OBJECTIVES: To compare three hypofractionated protocols in postmastectomy cancinoma breast in terms of local control, toxicity and work load. METHODS: A total of three hundred patients suffering from cancer breast stage T2-4, N any were randomized into three arms after mastectomy. All the patients were treated with four fields on Co60 i.e. two tangential portals for chest wall, one anterior supraclavicular and axillary field and a posterior axillary boost and were randomized into three arms i.e. 2700 CGy in 5 fractions (one week) arm A, 3500 CGy in 10 fractions (2 weeks) arm B and 4000 CGy in 15 fractions (3 weeks) arm C. Skin, cardiac, pulmonary and haematological toxicities and lymphoedema were compared in addition to local control and work load. RESULTS: The locoregional relapses were 11%, 12% and 10% in arms A, B and C respectively. 26%, 24% and 28% patients developed metastatic disease and 17%, 18% and 20% died in the three arms. G3 and G4 skin toxicities were 37%, 28% and 14%. G2 and G3 lymphedoema was 21%, 22% and 27%. Cardiac toxicity was 5%, 6% and 5% while pulmonary toxicity was 4%, 5% and 5% respectively. All the differences except skin toxicity were statistically insignificant. There were no cases of haematological depression or rib fractures. CONCLUSION: All the three short protocols were equally effective in locoregional disease control and toxicity was also comparable. They were helpful in reducing the work load and can be safely recommended for routine clinical use.

Molecular-Level "Observations" of the Behavior of Gold Nanoparticles in Aqueous Solution and Interacting with a Lipid Bilayer Membrane.

We use coarse-grained molecular dynamics simulations to "observe" details of interactions between ligand-covered gold nanoparticles and a lipid bilayer model membrane. In molecular dynamics simulations, one puts the individual atoms and groups of atoms of the physical system to be "observed" into a simulation box, specifies the forms of the potential energies of interactions between them (ultimately quantum based), and lets them individually move classically according to Newton's equations of motion, based on the forces arising from the assumed potential energy forms. The atoms that are chemically bonded to each other stay chemically bonded, following known potentials (force fields) that permit internal degrees of freedom (internal rotation, torsion, vibrations), and the interactions between nonbonded atoms are simplified to Lennard-Jones forms (in our case) and coulombic (where electrical charges are present) in which the parameters are previously optimized to reproduce thermodynamic properties or are based on quantum electronic calculations. The system is started out at a reasonable set of coordinates for all atoms or groups of atoms, and then permitted to develop according to the equations of motion, one small step (usually 10 fs time step) at a time, for millions of steps until the system is at a quasi-equilibrium (usually reached after hundreds of nanoseconds). We then let the system play out its motions further for many nanoseconds to observe the behavior, periodically taking snapshots (saving all positions and energies), and post-processing the snapshots to obtain various average descriptions of the system. Alkanethiols of various lengths serve as examples of hydrophobic ligands and methyl-terminated PEG with various numbers of monomer units serve as examples of hydrophilic ligands. Spherical gold particles of various diameters as well as gold nanorods form the core to which ligands are attached. The nanoparticles are characterized at the molecular level, especially the distributions of ligand configurations and their dependence on ligand length, and surface coverage. Self-assembly of the bilayer from an isotropic solution and observation of membrane properties that correspond well to experimental values validate the simulations. The mechanism of permeation of a gold NP coated with either a hydrophobic or a hydrophilic ligand, and its dependence on surface coverage, ligand length, core diameter, and core shape, is investigated. Lipid response such as lipid flip-flops, lipid extraction, and changes in order parameter of the lipid tails are examined in detail. The mechanism of permeation of a PEGylated nanorod is shown to occur by tilting, lying down, rotating, and straightening up. The nature of the information provided by molecular dynamics simulations permits understanding of the detailed behavior of gold nanoparticles interacting with lipid membranes which in turn helps to understand why some known systems work better than others and aids the design of new particles and improvement of methods for preparing existing ones.