Polyply; a python suite for facilitating simulations of macromolecules and nanomaterials

Molecular dynamics simulations play an increasingly important role in the rational design of (nano)-materials and in the study of biomacromolecules. However, generating input files and realistic starting coordinates for these simulations is a major bottleneck, especially for high throughput protocols and for complex multi-component systems. To eliminate this bottleneck, we present the polyply software suite that provides 1) a multi-scale graph matching algorithm designed to generate parameters quickly and for arbitrarily complex polymeric topologies, and 2) a generic multi-scale random walk protocol capable of setting up complex systems efficiently and independent of the target force-field or model resolution. We benchmark quality and performance of the approach by creating realistic coordinates for polymer melt simulations, single-stranded as well as circular single-stranded DNA. We further demonstrate the power of our approach by setting up a microphase-separated block copolymer system, and by generating a liquid-liquid phase separated system inside a lipid vesicle.

Polyacrylonitrile Nanofibers Containing Viroblock as Promising Material for Protective Clothing

Antimicrobial viroblock/polyacrylonitrile nanofiber webs fabricated using the electrospinning method were assessed in terms of the antimicrobial activity against infectious agents as a potential material used in mask production. Viroblock (VB) is an amalgam of lipid vesicle and silver. Lipid vesicle depletes the virus outer membrane, which contains cholesterol, while silver ions penetrate the virus, interact with sulfur-bearing moieties, and possess the virus bactericidal property. VB, having anti-coronavirus and anti-influenza properties, was prepared in four different concentrations, 0.5 wt%, 1 wt%, 1.5 wt%, and 2 wt%, in regard to nanofiber weight. The resultant nanofibers were characterized by scanning electron microscope (SEM), Fourier transform infrared (FTIR), thermogravimetric analysis (TGA), water contact angle, water content, and thermogravimetric analysis (TGA). Moreover, all nanofibrous samples were evaluated for cell proliferation assay and ATCC antibacterial tests. Based on characterization results and cytotoxicity, the developed composite nanofibers-based webs showed good promise for utilization in anti-viral masks. Particularly, 2 wt% VB/PAN nanofibers have the highest antibacterial properties against negative and positive bacteria along with excellent cell viability.

Lipid vesicle fusion as a vehicle to study transmembrane protein interactions

Alzheimer's disease, among other neurologically degenerative diseases, has been linked to protein-enzyme interactions that originate within the transmembrane domain of a cell. The lipid environment that houses these interactions lends difficulty to studying intramembrane interactions, often making for time consuming data analysis. Lengthy data interpretation on top of the rate in which protein-enzyme interactions take place creates a need for a method to overcome these obstacles. The use of lipid vesicle fusion to apply a margin of control over the time frame of interaction combined with deep probing spectroscopic techniques can minimize the interference of the lipid environment. Deep ultraviolent resonance Raman (dUVRR) is a vibrational spectroscopic technique that probes along the protein backbone that allows for removal of lipid environmental interference through background subtraction. Lipid vesicle fusion has been demonstrated by mixing lipid vesicles comprised of oppositely charged head groups (cationic 1,2-diaurroyl-sn-glycero-3-phospho-(1-rac-glycerol) (DLPG)) and anionic 1,2-dilauroyl-sn-glycero-3-ethylphocholine (12:0 EPC) or 1,2-dimyristoyl-sn-glycero-3-ethylphocholine (14:0 EPC)) of equivalent or varying aliphatic tail length, up to a 2-carbon difference. The fluorescent dye, 8-aminonapthalene 1,3,6-trisulfonic acid (ANTS), paired with the quencher, p-xylene-bis-pyridiumbromide (DPX), are separately encased in either DLPG or 12:0 EPC/14:0 EPC, respectively, in aqueous solution, and evidence of lipid vesicle fusion is provided by monitoring fluorescence intensity of ANTS as the two solutions are mixed, resulting in the closing proximity of ANTS and DPX observed as a decrease in fluorescence intensity. Additional evidence is provided by dynamic light scattering (DLS) measurements of both independent vesicle solutions and their mixture showing an increase in hydrodynamic radius (Rh). In addition, cohesion of similarly sized lipids is demonstrated, as DLPG (12-carbon chain) fails to fuse with cationic lipids of chain length 16 carbons or longer. Circular dichroism (CD) is a spectroscopic technique that uses left and right-handed polarized light to obtain the overall secondary structure of proteins. Shown is the use of CD to probe the secondary structure and the changes incurred on PolyLA7 (PLA7), a model ?-helical peptide when placed in a transmembrane or hydrophobic environment, through a change in the lipid environment. PLA7 was inserted in DLPG lipid vesicles and then mixed in solution with lipid vesicles comprised of 14:0 EPC. CD spectra were obtained pre and post vesicle fusion, demonstrating the use of lipid fusion as a means to combine membrane embedded proteins of interest while still being able to observe changes that take place. Finally, we propose an on-demand lipid fusion system in which two separate lipid vesicles could be co-suspended in solution and then chemically or photonically induced to fuse. A titration was performed to obtain the pKa of a synthesized pH inducible cationic lipid (pHiCL). The pHiCL is a dipicolylamine with an attached 12-carbon aliphatic tail. The pHiCL was titrated while suspended in an aqueous environment and while inserted into a lipid vesicle comprised of DLPC, a net neutral lipid also with a 12-carbon length aliphatic tail. The pHiCL will be the first component of a two-part system in which a photoacid (PA) will be used to protonate the pHiCL in solution giving rise to cationic and anionic surfaced lipid vesicles causing vesicle fusion to occur.

LOSS OF PLASMA MEMBRANE LIPID ASYMMETRY CAN INDUCE ORDERED DOMAIN (RAFT) FORMATION

The lipids in one leaflet of an asymmetric artificial lipid vesicle can induce or suppress the formation of ordered lipid domains (rafts) in the opposing leaflet. Whether suppression of domain formation might occur in plasma membranes was studied by using plasma membrane vesicles (PMVs) from RBL-2H3 cells. Ordered domain formation was assessed by FRET and fluorescence anisotropy. Ordered domains in PMV prepared by N-ethyl maleimide (NEM) treatment formed to some extent up to about 37oC. In contrast, ordered domains in symmetric vesicles formed from extracted PMV lipids were stable up to 55oC. This indicates that the stability of ordered domains was substantially less in the intact PMV. A similar decrease in ordered domain stability was observed in artificial asymmetric lipid vesicles relative to the corresponding symmetric vesicles. This suggested either that the intact PMV have a significant degree of lipid asymmetry or that PMV proteins suppress domain formation. Additional experiments ruled out the latter explanation. First, stabilization of ordered domain formation relative to intact PMV was observed in protein-containing symmetric vesicles prepared by detergent solubilization of intact PMV, followed by rapid dilution of detergent. Second, ordered domain stability in intact PMV was not altered after extensively removing PMV proteins with proteinase K. We conclude that intact NEM-induced PMV preserve a significant amount of the lipid asymmetry of plasma membranes, and that loss of PMV lipid asymmetry can induce ordered domain formation, consistent with the possibility that dynamic control of lipid asymmetry can regulate ordered domain formation in the plasma membrane.