All-atom de novo protein folding with a scalable evolutionary algorithm

The search for efficient and predictive methods to describe the protein folding process at the all-atom level remains an important grand-computational challenge. The development of multi-teraflop architectures, such as the IBM BlueGene used in this study, has been motivated in part by the large computational requirements of such studies. Here we report the predictive all-atom folding of the forty-amino acid HIV accessory protein using an evolutionary stochastic optimization technique. We implemented the optimization method as a master-client model on an IBM BlueGene, where the algorithm scales near perfectly from 64 to 4096 processors in virtual processor mode. Starting from a completely extended conformation, we optimize a population of 64 conformations of the protein in our all-atom free-energy model PFF01. Using 2048 processors the algorithm predictively folds the protein to a near-native conformation with an RMS deviation of 3.43 A in < 24 h.     

Glycal glycosylation and 2-nitroglycal concatenation, a powerful combination for mucin core structure synthesis

A 3,4-O-unprotected galactal derivative having bulky 6-O-TIPS protection (compound 2) could be regioselectively 3-O-glycosylated with O-(galactopyranosyl) trichloroacetimidates; depending on the protecting group pattern stereoselectively alpha- and beta-linked disaccharides were obtained. With O-(2-azido-2-deoxyglucopyransyl) trichloroacetimidate as donor (compound 10A), glycosylation of 2 and of a 6-O-unprotected galactal derivative led in acetonitrile as solvent exclusively to a beta(1-3)- and a beta(1-6)-linked disaccharide, respectively. Nitration of the galactal moieties of the saccharides followed by Michael-type addition of serine and threonine derivatives (7a,b) installed the alpha-galacto-configuration, thus readily furnishing O-glycosyl amino acid building blocks for the incorporation of core 1, core 2, core 3, core 6, and core 8 structures into glycopeptides. 2-Nitrogalactal and 2-nitroglucal derivatives could be also successfully employed in glycoside bond formation via Michael-type addition in a reiterative manner, affording the corresponding core 5, core 7, and core 6 building blocks. In this approach, highly stereoselective glycoside bond formations were based exclusively on Michael-type addition to the nitro-enol ether moiety of the 2-nitroglycals. Hence, 2-nitroglycals are versatile intermediates for base-catalyzed glycoside bond formation.     

Plasma-induced graft copolymerization of poly(methacrylic acid) on electrospun poly(vinylidene fluoride) nanofiber membrane

Electrospun nanofibrous membranes (ENM) which have a porous structure have a huge potential for various liquid filtration applications. In this paper, we explore the viability of using plasma-induced graft copolymerization to reduce the pore sizes of ENMs. Poly(vinylidene) fluoride (PVDF) was electrospun to produce a nonwoven membrane, comprised of nanofibers with diameters in the range of 200-600 nm. The surface of the ENM was exposed to argon plasma and subsequently graft-copolymerized with methacrylic acid. The effect of plasma exposure time on grafting was studied for both the ENM and a commercial hydrophobic PVDF (HVHP) membrane. The grafting density was quantitatively measured with toluidine blue-O. The degree of grafting increased steeply with an increase in plasma exposure time for the ENM, attaining a maximum of 180 nmol/mg after 120 s of plasma treatment. However, the increase in the grafting density on the surface of the HVHP membrane was not as drastic, reaching a plateau of 65 nmol/mg after 60 s. The liquid entry permeation of water dropped extensively for both membranes, indicating a change in surface properties. Field emission scanning electron microscopy micrographs revealed an alteration in the surface pore structure for both membranes after grafting. Bubble point measurements of the ENM reduced from 3.6 to 0.9 um after grafting. The pore-size distribution obtained using the capillary flow porometer for the grafted ENM revealed that it had a similar profile to that of a commercial hydrophilic commercial PVDF (HVLP) membrane. More significantly, water filtration studies revealed that the grafted ENM had a better flux throughput than the HVLP membrane. This suggests that ENMs can be successfully engineered through surface modification to achieve smaller pores while retaining their high flux performance.     

Self-assembled hybrid polymer-TiO2 nanotube array heterojunction solar cells

Films comprised of 4 microm long titanium dioxide nanotube arrays were fabricated by anodizing Ti foils in an ethylene glycol based electrolyte. A carboxylated polythiophene derivative was self-assembled onto the TiO2 nanotube arrays by immersing them in a solution of the polymer. The binding sites of the carboxylate moiety along the polymer chain provide multiple anchoring sites to the substrate, making for a stable rugged film. Backside illuminated liquid junction solar cells based on TiO2 nanotube films sensitized by the self-assembled polymeric layer showed a short-circuit current density of 5.5 mA cm-2, a 0.7 V open circuit potential, and a 0.55 fill factor yielding power conversion efficiencies of 2.1% under AM 1.5 sun. A backside illuminated single heterojunction solid state solar cell using the same self-assembled polymer was demonstrated and yielded a photocurrent density as high as 2.0 mA cm-2. When a double heterojunction was formed by infiltrating a blend of poly(3-hexylthiophene) (P3HT) and C60-methanofullerene into the self-assembled polymer coated nanotube arrays, a photocurrent as high as 6.5 mA cm-2 was obtained under AM 1.5 sun with a corresponding efficiency of 1%. The photocurrent action spectra showed a maximum incident photon-to-electron conversion efficiency (IPCE) of 53% for the liquid junction cells and 25% for the single heterojunction solid state solar cells.     

Solvent-free synthesis of heterocyclic compounds using microwaves

Microwave-enhanced solvent-free synthetic approach is described that features simplicity, manipulative ease of the operation and conservation of solvents as the main advantages. This eco-friendly approach, which has found application in facile organic functional group transformations, is applied to rapid assembly of heterocyclic compounds. A variety of solid state reactions are described that occur rapidly at ambient pressure under solventless conditions and provide ready access to intermediates such as enamines and α-tosyloxyketones which can be transformed in situ to biologically significant heterocyclic compounds such as isoflav-3-enes, flavones, quinolones, 2-aroylbenzo[b]furans and thiazoles in one-pot operation. Multicomponent reactions under these solvent-free conditions can be adapted for high speed parallel synthesis and are exemplified by assembly of dihydropyrimidine-2(1H)-ones (Biginelli reaction) and imidazo[1,2-a]annulated pyridines, pyrazines and pyrimidines (Ugi reaction) which may have potential in building a library of such compounds.     

Thermal Behaviour of Glycidyl Methacrylate Homopolymers and Copolymers

The paper describes the effect of molecular mass and copolymer composition on thermal behaviour of homopolymers and copolymers of glycidyl methacrylate and methyl methacrylate. The polymerisation was done by using group transfer polymerization (GTP) and free radical techniques. A multistep decomposition was observed in polymers prepared by free radical technique indicating the presence of weak linkages in the backbone. Copolymers prepared by GTP had fewer weak sites and degraded in single step by a random chain scission.This revised version was published online in November 2005 with corrections to the Cover Date.     

Imaging in turbid media using quasi-ballistic photons

We study by means of experiments and Monte Carlo simulations, the scattering of light in random media, to determine the distance up to which photons travel along almost undeviated paths within a scattering medium, and are therefore capable of casting a shadow of an opaque inclusion embedded within the medium. Such photons are isolated by polarisation discrimination wherein the plane of linear polarisation of the input light is continuously rotated and the polarisation preserving component of the emerging light is extracted by means of a Fourier transform. This technique is a software implementation of lock-in detection. We find that images may be recovered to a depth far in excess of that predicted by the diffusion theory of photon propagation. To understand our experimental results, we perform Monte Carlo simulations to model the random walk behaviour of the multiply scattered photons. We present a new definition of a diffusing photon in terms of the memory of its initial direction of propagation, which we then quantify in terms of an angular correlation function. This redefinition yields the penetration depth of the polarisation preserving photons. Based on these results, we have formulated a model to understand shadow formation in a turbid medium, the predictions of which are in good agreement with our experimental results.     

High energy binders: glycidyl azide and allyl azide polymer

Hydroxy-terminated azido polymers such as poly(glycidyl azide), poly bis(azidomethyl oxetane) and poly(azidomethyl methyloxetane) have been investigated in the past in propellent formulations and as fuels in rocket technology. The high energy released upon the decomposition of the azido group is responsible for their specialized application as high-energy binders. The present paper describes the synthesis and characterization of new low molecular mass azido polymer i.e. poly(allyl azide). The curing reaction was carried out by using 1,3-cyclic dipolar addition reaction. The dipolarophiles, such as dimethylene glycol dimethacrylate (EGDMA) and addition polyimides (bismaleimides, bisnadimides and bisitaconimides) were used for curing of azido polymers. The curing reaction was monitored by FT-IR and differential scanning calorimetry. Curing was carried out at 40°C for 16 h (EGDMA) or 2 days (bismaleimide) and then at 60°C by using different phr of dipolarophiles. The heat of exothermic transition, due to decomposition of azide groups and thermal polymerization of addition polyimides, was very high and an improvement in thermal stability of cured resins was observed.     

Propagation velocity of the reaction front in addition polymerization systems

Traveling polymerization fronts in unstirred solutions of methylmethacrylate, methacrylic acid, or acrylamide with some free radicals initiators (through thermal decomposition) have been observed experimentally. A local heating of the initial reactant mixture, under suitable conditions, leads to a reaction front that propagates along the space coordinate with a constant velocity. In this article, a physical interpretation of this phenomenon is provided through a mathematical model that accounts for the depolimerization reaction and is based on the constant pattern approach. Moreover, an approximate explicit analytic expression for the velocity of propagation of the polymerization front is proposed. The theoretical values are compared with those measured experimentally as a function of the initiator concentration for different addition polymerization systems. © 1997 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 35:1047–1059, 1997