Interface Water Assists in Dimethyl Sulfoxide Crossing and Poration in Model Bilayer.

Understanding the mechanism of transport and pore formation by a commonly used cryoprotectant, dimethyl sulfoxide (DMSO), across cell membranes is fundamentally crucial for drug delivery and cryopreservation. To shed light on the mechanism and thermodynamics of pore formation and crossing behavior of DMSO, extensive all-atom molecular dynamics simulations of 1,2-dimyristoyl-rac-glycero-3-phosphocholine (DMPC) bilayers are performed at various concentrations of DMSO at a temperature above the physiological temperature. Our results unveil that DMSO partially depletes water from the interface and positions itself between lipid heads without full dehydration. This induces a larger area per headgroup, increased disorder, and enhanced fluidity without any disintegration even at the highest DMSO concentration studied. The enhanced disorder fosters local fluctuations at the interface that nucleate dynamic and transient pores. The potential of mean force (PMF) of DMSO crossing is derived from two types of biased simulations: a single DMSO pulling using the umbrella sampling technique and a cylindrical pore formation using the recently developed chain reaction coordinate method. In both cases, DMSO crossing encounters a barrier attributed to unfavorable polar nonpolar interactions between DMSO and lipid tails. As the DMSO concentration increases, the barrier height reduces along with the faster lateral and perpendicular diffusion of DMSO suggesting favorable permeation. Our findings suggest that the energy required for pore formation decreases when water assists in the formation of DMSO pores. Although DMSO displaces water from the interface toward the far interface region without complete dehydration, the presence of interface water diminishes pore formation free energy. The existence of interface water leads to the formation of a two-dimensional percolated water-DMSO structure at the interface, which is absent otherwise. Overall, these insights into the mechanism of DMSO crossing and pore formation in the bilayer will contribute to understanding cryoprotectant behavior under supercooled conditions in the future.

Aspirin-Induced Ordering and Faster Dynamics of a Cationic Bilayer for Drug Encapsulation.

The lipid dynamics and phase play decisive roles in drug encapsulation and delivery to the intracellular target. Thus, understanding the dynamic and structural alterations of membranes induced by drugs is essential for targeted delivery. To this end, united-atom molecular dynamics simulations of a model bilayer, dioctadecyldimethylammonium bromide (DODAB), are performed in the absence and presence of the usual nonsteroidal anti-inflammatory drug (NSAID), aspirin, at 298, 310, and 345 K. At 298 and 310 K, the bilayers are in the interdigitated two-dimensional square phases, which become rugged in the presence of aspirin, as evident from height fluctuations. At 345 K, the bilayer is in the fluid phase in both the absence and presence of aspirin. Aspirin is preferentially located near the oppositely charged headgroup and creates void space, which leads to an increase in the interdigitation and order parameters. Although the center of mass of lipids experiences structural arrest, they reach the diffusive regime faster and have higher lateral diffusion constants in the presence of aspirin. Results are found to be consistent with recent quasi-elastic neutron scattering studies that reveal that aspirin acts as a plasticizer and enhances lateral diffusion of lipids in both ordered and fluid phases. Different relaxation time scales of the bonds along the alkyl tails of DODAB due to the multitude of lipid motions become faster upon the addition of aspirin. Our results show that aspirin insertion is most favorable at physiological temperature. Thus, the ordered, more stable, and faster DODAB bilayer can be a potential drug carrier for the protected encapsulation of aspirin, followed by targeted and controlled drug release with antibacterial activity in the future.

Thylakoid Composition Facilitates Chlorophyll a Dimerization through Stronger Interlipid Interactions.

Plant thylakoid membrane serves as a crucial matrix for the aggregation of chlororophyll a (CLA) pigments, essential for light harvesting. To understand the role of lipid compositions in the stability of CLA aggregates, dimerization of chlorophyll a molecules (CLA) is studied in the presence of the thylakoid and the bilayers comprising either the least or the highest unsaturated lipids by using coarse-grained molecular dynamics simulations. The thylakoid membrane enhances the stability of the CLA dimer compared with other membranes due to very strong lipid-lipid interactions. The thylakoid exhibits a distinct distribution of lipids around the CLA dimer. Less unsaturated lipids reside in close proximity to the dimer, promoting increased order and efficient packing. Conversely, higher unsaturated lipids are depleted from the dimer, imparting flexibility to the membrane. The combination of tight packing near the dimer and membrane flexibility away from the dimer enhances the stability of the dimer in the thylakoid membrane. Our results suggest that lipid mixing, rather than lipid unsaturation, plays a critical role in facilitating CLA dimerization by modulating the membrane microenvironment through stronger lipid-lipid interactions. These insights will be useful in understanding how lipid compositions affect efficient light absorption and energy transfer during photosynthesis in the future.

Harnessing the hydrogen evolution reaction (HER) through the electrical mobility of an embossed Ag(I)-molecular cage and a Cu(II)-coordination polymer.

A structurally characterized porous Ag(I)-molecular cage AgMOC and a Cu(II)-coordination polymer CuCP with a pre-synthesized ligand 1,3-bis(((E)-2-methoxybenzylidene)amino)propan-2-ol and its parental amine with thiocyanate are reported to harness electrical mobility-driven hydrogen evolution activity. Porosity-induced electrically conductive AgMOC emerges as a better electrocatalyst with a Tafel slope of 104 mV per decade over Cu(II)-polymer's slope of 128 mV per decade. The electrochemical stability and durability of the designed electrocatalysts in harnessing the HER activity are also examined under experimental conditions.

Aggregation of chlorophylls on plant thylakoid membranes using coarse-grained simulations.

Chlorophyll a (CLA) molecules in light-harvesting complexes are the most essential pigments for photosynthesis. Coarse-grained molecular dynamics simulations of CLA are carried out in plant thylakoid membranes at 293 K by varying the total lipid-to-CLA ratio using our previously derived coarse-grained model of CLA and MARTINI force fields for lipids. Our simulations show that CLA molecules dynamically form aggregates that break and reform. The lifetime of the dimer and the waiting time of the dimer formation follow bi-exponential distributions for the higher concentrations of CLA. The number of aggregates increases with an increasing concentration of CLA, where the aggregation is governed by van der Waals interactions. Our simulations suggest that selective lipids promote the formation of CLA aggregates in plant thylakoid membranes. As the concentration of CLA increases, diacylglycerol and phosphatidylglycerol lipids with palmitoyl tails prefer to reside near the CLA aggregates, and the lipids with linolenoyl tails with higher levels of unsaturation move away from the aggregates. Such preferential locations of lipids result in increasing lateral heterogeneity in the order parameter and density with increasing CLA concentration. This induces more undulations in membranes, resulting in a lower bending modulus and area compressibility. Our work unfolds the mechanism of the formation of CLA aggregates and their effect on the structure of thylakoid bilayers. The study provides the foundation for a better understanding of more complex biophysical phenomena, such as photosynthesis and non-photochemical quenching, in the future.

Relaxation time scales of interfacial water upon fluid to ripple to gel phase transitions of bilayers.

The slow relaxation of interface water (IW) across three primary phases of membranes is relevant to understand the influence of IW on membrane functions at supercooled conditions. To this objective, a total of ∼16.26µs all-atom molecular dynamics simulations of 1,2-dimyristoyl-sn-glycerol-3-phosphocholine lipid membranes are carried out. A supercooling-driven drastic slow-down in heterogeneity time scales of the IW is found at the fluid to the ripple to the gel phase transitions of the membranes. At both fluid-to-ripple-to-gel phase transitions, the IW undergoes two dynamic crossovers in Arrhenius behavior with the highest activation energy at the gel phase due to the highest number of hydrogen bonds. Interestingly, the Stokes-Einstein (SE) relation is conserved for the IW near all three phases of the membranes for the time scales derived from the diffusion exponents and the non-Gaussian parameters. However, the SE relation breaks for the time scale obtained from the self-intermediate scattering functions. The behavioral difference in different time scales is universal and found to be an intrinsic property of glass. The first dynamical transition in the α relaxation time of the IW is associated with an increase in the Gibbs energy of activation of hydrogen bond breaking with locally distorted tetrahedral structures, unlike the bulk water. Thus, our analyses unveil the nature of the relaxation time scales of the IW across membrane phase transitions in comparison with the bulk water. The results will be useful to understand the activities and survival of complex biomembranes under supercooled conditions in the future.

Quantifying dynamical heterogeneity length scales of interface water across model membrane phase transitions.

All-atom molecular dynamics simulations of 1,2-dimyristoyl-sn-glycero-3-phosphocholine lipid membranes reveal a drastic growth in the heterogeneity length scales of interface water (IW) across fluid to ripple to gel phase transitions. It acts as an alternate probe to capture the ripple size of the membrane and follows an activated dynamical scaling with the relaxation time scale solely within the gel phase. The results quantify the mostly unknown correlations between the spatiotemporal scales of the IW and membranes at various phases under physiological and supercooled conditions.

Supramolecular encapsulation of nanocrystalline Schiff bases into ß-cyclodextrin for multifold enrichment of bio-potency.

We report the solvent-free green synthesis of two Schiff bases, (E)-2-((2-hydroxy-3-methoxybenzylidene)amino)-4-methylphenol (SL1) and (E)-2-((2-hydroxybenzylidene) amino)-4-methylphenol (SL2), and their inclusion complexes with ß-cyclodextrin (ß-CD). The encapsulation phenomenon, structural characteristics and hydrolytic stabilities of the SL1, SL2 and their inclusion complexes are determined with a suite of spectroscopic, analytical and crystallographic analyses. Dose and time-dependent cytotoxicity study of SL1-ß-CD and SL2-ß-CD against two breast cancer cell lines, Michigan Cancer Foundation-7 (MCF-7) and metastatic mammary adenocarcinoma1 (MDA-MB-231), exhibit excellent inhibitory activity with significant non-cytotoxic concentrations and ensure a multifold elevation of bio-potency than the parent Schiff base compounds. The Annexin-V assay determines the efficacy of these inclusion complexes to trigger apoptosis, suggesting that SL2-ß-CD possesses better efficacy as an anti-cancer drug. To the best of our knowledge, we, for the first time, report the inclusion of nanocrystalline Schiff bases into ß-CD for multifold enrichment of bio-potency.

Development of a hydrolase mimicking peptide amphiphile and its immobilization on silica surface for stereoselective and enhanced catalysis.

Biocatalysis is an important area of modern research and is extensively explored by various industries to attain greener methods in various applications. Supramolecular interactions of short peptides have been under the scanner for developing artificial smart materials inspired from natural systems. Peptide-based artificial enzymes have been proved to show various enzyme-like activities. Therefore, immobilization of catalytic peptides on solid surfaces can be an extremely useful breakthrough for development of cost-effective catalytic formulations. In this work, a series of peptide amphiphiles (PAs) have been systematically analyzed to find the most effective catalyst with esterase like activity. The PA, containing a catalytic triad, 'Asp(Ser)His' in a branched manner, was further immobilized onto silica nanoparticles through covalent bonding method to obtain surface coated catalytic silica nanoparticles. The heterogenous catalytic formulation not only showed enhanced esterase activity than the self-assembled PA in homogenous phase, but also exceeded the activity of natural CV lipase. The catalytic formulation showed high stereoselectivity towards chiral esters. Moreover, the catalyst remained stable at higher temperature, in presence of various denaturant and retained its activity after several catalytic cycles. The ease of separation, robust nature, reusability and high stereoselectivity of the catalyst opens up the possibility of creating new generation heterogeneous catalysts for further industrial applications.

Dehydration induced dynamical heterogeneity and ordering mechanism of lipid bilayers.

Understanding the influence of dehydration on the membrane structure is crucial to control membrane functionality related to domain formation and cell fusion under anhydrobiosis conditions. To this end, we perform all-atom molecular dynamic simulations of 1,2-dimyristoyl-sn-glycero-3-phosphocholine dimyristoylphosphatidylcholine lipid membranes at different hydration levels at 308 K. As dehydration increases, the lipid area per head group decreases with an increase in bilayer thickness and lipid order parameters indicating bilayer ordering. Concurrently, translational and rotational dynamics of interfacial water (IW) molecules near membranes slow down. On the onset of bilayer ordering, the IW molecules exhibit prominent features of dynamical heterogeneity evident from non-Gaussian parameters and one-dimensional van Hove correlation functions. At a fully hydrated state, diffusion constants (D) of the IW follow a scaling relation, D∼τα -1, where the α relaxation time (τα) is obtained from self-intermediate scattering functions. However, upon dehydration, the relation breaks and the D of the IW follows a power law behavior as D∼τα -0.57, showing the signature of glass dynamics. τα and hydrogen bond lifetime calculated from intermittent hydrogen bond auto-correlation functions undergo a similar crossover in association with bilayer ordering on dehydration. The bilayer ordering is accompanied with an increase in fraction of caged lipids spanned over the bilayer surface and a decrease in fraction of mobile lipids due to the non-diffusive dynamics. Our analyses reveal that the microscopic mechanism of lipid ordering by dehydration is governed by dynamical heterogeneity. The fundamental understanding from this study can be applied to complex bio-membranes to trap functionally relevant gel-like domains at room temperature.

A Comparative Study on DMSO-Induced Modulation of the Structural and Dynamical Properties of Model Bilayer Membranes.

Modulating the structures and properties of biomembranes via permeation of small amphiphilic molecules is immensely important, having diverse applications in cell biology, biotechnology, and pharmaceuticals, because their physiochemical and biological interactions lead to new pathways for transdermal drug delivery and administration. In this work, we have elucidated the role of dimethyl sulfoxide (DMSO), broadly used as a penetration-enhancing agent and cryoprotective agent on model lipid membranes, using a combination of fluorescence microscopy and time-resolved fluorescence spectroscopy. Spatially resolved fluorescence lifetime imaging microscopy (FLIM) has been employed to unravel how the fluidity of the DMSO-induced bilayer regulates the structural alteration of the vesicles. Moreover, we have also shown that the dehydration effect of DMSO leads to weakening of the hydrogen bond between lipid headgroups and water molecules and results in faster solvation dynamics as demonstrated by femtosecond time-resolved fluorescence spectroscopy. It has been gleaned that the water dynamics becomes faster because bilayer rigidity decreases in the presence of DMSO, which is also supported by time-resolved rotational anisotropy measurements. The enhanced diffusivity and increased membrane fluidity in the presence of DMSO are further ratified at the single-molecule level through fluorescence correlation spectroscopy (FCS) measurements. Our results indicate that while the presence of DMSO significantly affects the 1,2-dimyristoyl-rac-glycero-3-phosphocholine (DMPC) and 1,2-dipalmitoyl-rac-glycero-3-phosphatidylcholine (DPPC) bilayers, it has a weak effect on 1,2-dimyristoyl-sn-glycero-3-phospho-rac-glycerol (DMPG) vesicles, which might explain the preferential interaction of DMSO with the positively charged choline group present in DMPC and DPPC vesicles. The experimental findings have also been further verified with molecular dynamics simulation studies. Moreover, it has been observed that DMSO is likely to have a differential effect on heterogeneous bilayer membranes depending on the structure and composition of their headgroups. Our results illuminate the importance of probing the lipid structure and composition of cellular membranes in determining the effects of cryoprotective agents.

Interactions Determining the Structural Integrity of the Trimer of Plant Light Harvesting Complex in Lipid Membranes.

The structural basis for the stability of the trimeric form of the light harvesting complex (LHCII), a pigmented protein from green plants pivotal for photosynthesis, remains elusive till date. The protein embedded in a dipalmitoylphosphatidylcholine (DPPC) lipid membrane is investigated using all-atom molecular dynamics simulations to find out the interactions responsible for the structural integrity of the trimer and its relation to antenna function. Central association of chlorophyll a (CLA) molecules near the LHCII chains is attributed to a conserved coordination between the Mg of CLA and the oxygen of a specific residue of the first helix of a chain. The residue forms a salt-bridge with the fourth helix of the same chain of the trimer, not of the monomer. In an earlier experiment, three residues (WYR) at each chain of the trimer have been found indispensable for the trimerization and referred to as trimerization motif. We find that the residues of the trimerization motif are connected to the lipids or pigments by a chain of interactions rather than a direct contact. Synergistic effects of sequentially located hydrogen bonds and salt-bridges within monomers of the trimer keep the trimer conformation stable in association with the pigments or the lipids. These interactions are exclusively present in the pigmented trimer and not present in the monomer or in the unpigmented trimer. Thus, our results provide a molecular basis for the inherent stability of the LHCII trimer in a lipid membrane and explain many pre-existing experimental data.

Modulation of Membrane Fluidity to Control Interfacial Water Structure and Dynamics in Saturated and Unsaturated Phospholipid Vesicles.

The structure and dynamics of interfacial water in biological systems regulate the biochemical reactions. But, it is still enigmatic how the behavior of the interfacial water molecule is controlled. Here, we have investigated the effect of membrane fluidity on the structure and dynamics of interfacial water molecules in biologically relevant phopholipid vesicles. This study delineates that modulation of membrane fluidity through interlipid separation and unsaturation not only mitigate membrane rigidity but also disrupt the strong hydrogen bond (H-bond) network around the lipid bilayer interface. As a result, a disorder in H-bonding between water molecules arises several layers beyond the first hydration shell of the polar headgroup, which essentially modifies the interfacial water structure and dynamics. Furthermore, we have also provided evidence of increasing transportation through these modulated membranes, which enhance the membrane mediated isomerization reaction rate.

Dynamic coupling of a hydration layer to a fluid phospholipid membrane: intermittency and multiple time-scale relaxations.

Understanding the coupling of a hydration layer and a lipid membrane is crucial to gaining access to membrane dynamics and understanding its functionality towards various biological processes. To find out how significant the mutual influence of the hydration layer and bilayer dynamics is, a fully hydrated 1,2-dimyristoyl-sn-glycero-3-phosphorylcholine (DMPC) lipid bilayer is simulated atomistically in the presence of the TIP4P/2005 water model at 308 K. Interface water (IW) molecules are classified based on their continuous physical proximity or ability to form hydrogen bonds with different moieties of lipid heads. A gradient in retardation of translational mean square displacements is found to operate coherently for both IW and lipid components across the bilayer normal. Deviations from Gaussianity in van Hove correlation functions increase for the lipids and decrease for the IW from the tails to the heads. The IW molecules exhibit Fickian but intermittent dynamics due to coupled vibrations in the local cage formed by the hydrogen bonds with the lipid heads followed by decoupled translational jumps. Importantly, the differences in regional dynamics of lipid heads are clearly reflected in the dynamics of spatially resolved IW molecules physically close to the lipid heads, but not to the dynamics of the hydrogen bonded IW molecules far from the lipid heads. These analyses imply that spatially resolved interface water dynamics can act as a sensitive reflector of regional membrane dynamics occurring at sub ps to hundreds of ps time-scales for several important biological functions at physiological temperature in the future.

Asymmetry and Rippling in Mixed Surfactant Bilayers from All-Atom and Coarse-Grained Simulations: Interdigitation and Per Chain Entropy†.

Understanding lateral organizations of self-assembled bilayers is crucial to gain a control on functionally relevant topologies. We study self-assembled bilayers composed of a surfactant, behenyl trimethyl ammonium chloride (BTMAC), a cosurfactant, stearyl alcohol (SA), at a ratio of 2:1 in the presence of water at 283 K employing subsequent all-atom (AA) and coarse-grained (CG) molecular dynamics simulations. Differences in initial configurations lead to the formation of bilayers at ripple or square phases or interdigitated gel phases of varying trans-leaflet asymmetry. The AA ripple and gel phases are reproduced well at the CG level using bonded potentials from Boltzmann inversion of AA canonical sampling and nonbonded potentials from MARTINI. Inhomogeneous populations of disordered chains with higher per chain configurational entropy and tilt result in rippling stabilized by periodic hydrophobic energy barrier and strong interdigitation. Order parameters of the asymmetric bilayers are sufficiently coupled to the per chain entropies at both levels of resolutions to serve as a reflector of the per chain configurational entropy inaccessible by experiments. Thus, trans-bilayer asymmetry may be a controlling parameter to induce rippling in a bilayer of industrial importance. This work will be useful for future investigation on domain-associated transport and signaling in biomembranes at a low temperature.

Quantification of spatio-temporal scales of dynamical heterogeneity of water near lipid membranes above supercooling.

A hydrated 1,2-dimyristoyl-sn-glycero-3-phosphorylcholine (DMPC) lipid membrane is investigated using an all atom molecular dynamics simulation at 308 K to determine the physical sources of universal slow relaxations of hydration layers and length-scale of the spatially heterogeneous dynamics. Continuously residing interface water (IW) molecules hydrogen bonded to different moieties of lipid heads in the membrane are identified. The non-Gaussian parameters of all classes of IW molecules show a cross-over from cage vibration to translational diffusion. A significant non-Gaussianity is observed for the IW molecules exhibiting large length correlations in translational van Hove functions. Two time-scales for the ballistic motions and hopping transitions are obtained from the self intermediate scattering functions of the IW molecules with an additional long relaxation, which disappears for bulk water. The long relaxation time-scales for the IW molecules obtained from the self intermediate scattering functions are in good accordance with the hydrogen bond relaxation time-scales irrespective of the nature of the chemical confinement and the confinement lifetime. Employing a block analysis approach, the length-scale of dynamical heterogeneities is captured from a transition from non-Gaussianity to Gaussianity in van Hove correlation functions of the IW molecules. The heterogeneity length-scale is comparable to the wave-length of the small and weak undulations of the membrane calculated by Fourier transforms of lipid tilts. This opens up a new avenue towards a possible correlation between heterogeneity length-scale and membrane curvature more significant for rippled membranes. Thus, our analyses provide a measure towards the spatio-temporal scale of dynamical heterogeneity of confined water near membranes.

Unusual confinement properties of a water insoluble small peptide hydrogel.

Unlike polymeric hydrogels, in the case of supramolecular hydrogels, the cross-linked network formation is governed by non-covalent forces. Hence, in these cases, the gelator molecules inside the network retain their characteristic physicochemical properties as no covalent modification is involved. Supramolecular hydrogels thus get dissolved easily in aqueous medium as the dissolution leads to a gain in entropy. Thus, any supramolecular hydrogel, insoluble in bulk water, is beyond the present understanding and hitherto not reported as well. Herein, we present a peptide-based (PyKC) hydrogel which remained insoluble in water for more than a year. Moreover, in the gel state, any movement of solvent or solute to and from the hydrogel is highly restricted resulting in a high degree of compartmentalization. The hydrogel could be re-dissolved in the presence of some biomolecules which makes it a prospective material for in vivo applications. Experimental studies and all atom molecular dynamics simulations revealed that a cysteine containing gelator forms dimers through disulfide linkage which self-assemble into PyKC layers with a distinct PyKC-water interface. The hydrogel is stabilized by intra-molecular hydrogen bonds within the peptide-conjugates and the π-π stacking of the pyrene rings. The unique confinement ability of the hydrogel is attributed to the slow dynamics of water which remains confined in the core region of PyKC via hydrogen bonds. The hydrogen bonds present in the confined water need activation energies to move through the water depleted hydrophobic environment of pyrene rings which significantly reduces water transport across the hydrogel. The compartmentalizing ability is effectively used to protect enzymes for a long time from denaturing agents like urea, heat or methanol. Overall, the presented system shows unique insolubility and confinement properties that could be a milestone in the research of soft-materials.

Solvent Assisted Tuning of Morphology of a Peptide-Perylenediimide Conjugate: Helical Fibers to Nano-Rings and their Differential Semiconductivity.

Understanding the regulatory factors of self-assembly processes is a necessity in order to modulate the nano-structures and their properties. Here, the self-assembly mechanism of a peptide-perylenediimide (P-1) conjugate in mixed solvent systems of THF/water is studied and the semiconducting properties are correlated with the morphology. In THF, right handed helical fibers are formed while in 10% THF-water, the morphology changes to nano-rings along with a switch in the helicity to left-handed orientation. Experimental results combined with DFT calculations reveal the critical role of thermodynamic and kinetic factors to control these differential self-assembly processes. In THF, P-1 forms right handed helical fibers in a kinetically controlled fashion. In case of 10% THF-water, the initial nucleation of the aggregate is controlled kinetically. Due to differential solubility of the molecule in these two solvents, elongation of the nuclei into fibers is restricted after a critical length leading to the formation of nano-rings which is governed by the thermodynamics. The helical fibers show superior semi-conducting property to the nano-rings as confirmed by conducting-AFM and conventional I-V characteristics.

Trigonella seed extract ameliorates inflammation via regulation of the inflammasome adaptor protein, ASC.

Trigonella foenum-graecum (fenugreek) is an important medicinal plant, well known for its anti-inflammatory properties. However, the underlying cellular and molecular mechanisms of its action remain largely unknown. The apoptosis associated speck like protein containing a caspase recruitment domain (CARD) (ASC) is central to inflammatory and cell death pathways in innate and adaptive immunity. Here, we show that fenugreek seed extract provides cytoprotection to bacterial lipopolysaccharide (LPS) inflammed and nanosilica-treated fibroblasts via a reactive oxygen species independent pathway. All atom molecular dynamics simulations of ASC-ligand complex reveal that individual phytochemicals in fenugreek can bind to ASC via specific non-covalent interactions. These data show that a synergistic effect of fenugreek phytochemicals with the ASC protein alters its molecular properties resulting in altered cellular function. Such information is crucial to the development of targeted therapeutic interventions for inflammatory diseases.

Derivation of coarse-grained simulation models of chlorophyll molecules in lipid bilayers for applications in light harvesting systems.

The correct interplay of interactions between protein, pigment and lipid molecules is highly relevant for our understanding of the association behavior of the light harvesting complex (LHCII) of green plants. To cover the relevant time and length scales in this multicomponent system, a multi-scale simulation ansatz is employed that subsequently uses a classical all atomistic (AA) model to derive a suitable coarse grained (CG) model which can be backmapped into the AA resolution, aiming for a seamless conversion between two scales. Such an approach requires a faithful description of not only the protein and lipid components, but also the interaction functions for the indispensable pigment molecules, chlorophyll b and chlorophyll a (referred to as chl b/chl a). In this paper we develop a CG model for chl b and chl a in a dipalmitoylphosphatidyl choline (DPPC) bilayer system. The structural properties and the distribution behavior of chl within the lipid bilayer in the CG simulations are consistent with those of AA reference simulations. The non-bonded potentials are parameterized such that they fit to the thermodynamics based MARTINI force-field for the lipid bilayer and the protein. The CG simulation shows chl aggregation in the lipid bilayer which is supported by fluorescence quenching experiments. It is shown that the derived chl model is well suited for CG simulations of stable, structurally consistent, trimeric LHCII and can in the future be used to study their large scale aggregation behavior.