Density functional theory and molecular dynamics investigations on substituted banana-shaped compounds

Density functional theory (DFT) calculations and molecular dynamics (MD) simulations on the atomic level were performed on three different substituted banana-shaped compounds derived from 1,3-phenylene bis[4-(4-n-hexyloxyphenyliminomethyl)benzoate] (P-6-O-PIMB). The DFT studies were carried out on the isolated molecules, and in the MD simulations clusters were treated with up to 64 monomers. The effect of polar substituents, such as chlorine and the nitro group, on the central 1,3-phenylene unit of banana-shaped compounds was investigated. In particular, flexibility, polarity, electrostatic potential (ESP) group charge distributions, B-factors, bending angles and molecular lengths were considered. The MD results were analysed by trajectories of significant torsion angles as well as order parameters such as radial atom pair distribution functions g(r), orientational correlation functions g(o), diffusion coefficients (D) and root mean square deviations (RMSD) values. The g(r) and g(o) values show that a certain long range order is generated by the introduction of a NO₂ group in the 2-position of the central 1,3-phenylene ring. In contrast, the chlorination at the 4 and 6 positions of the central 1,3-phenylene unit decreases the long range order tendency by its perturbation effect on the conformations in such molecules. Moreover, g(r) and g(o) values, as well as diffusion coefficients, show that in the NO₂ substituted compound the formation of microphase areas is preferred. Finally, the aggregation effect in such compounds was studied in a systematic way by a comparison of the conformational properties of the isolated molecules and the monomers in the clusters. Figure Molecular dynamics (MD) simulations on the aggregation behaviour of substituted banana-shaped compounds Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Proteomic approach for identification and characterization of novel immunostimulatory proteins from soluble antigens of Leishmania donovani promastigotes

Visceral leishmaniasis (VL) caused by Leishmania donovani is a major parasitic disease prevalent in endemic regions of Bihar in India. In the absence of good chemotherapeutic options, there is a need to develop an effective vaccine against VL which should be dependent on the generation of a T helper type 1 (Th1) immune response. We have shown that soluble proteins from promastigote of a new clinical isolate of L. donovani (2001) ranging from 68 to 97.4 kDa (F2 fraction), induce Th1 responses in the peripheral blood mononuclear cells of cured Leishmania patients and hamsters and also showed significant prophylactic potential. To understand the nature of F2 proteins, it was further characterized using 2-DE, MALDI-TOF and MALDI-TOF/TOF-MS. In all, 63 spots were cut from a CBB stained gel for analysis and data was retrieved for 52 spots. A total of 33 proteins were identified including six hypothetical/unknown proteins. Major immunostimulatory proteins were identified as elongation factor-2, p45, heat shock protein (HSP)70, HSP83, aldolase, enolase, triosephosphate isomerase, protein disulfideisomerase and calreticulin. This study substantiates the usefulness of proteomics in characterizing a complex protein fraction (F2) map of soluble L. donovani promastigote antigen identified as Th1 stimulatory for its potential as vaccine targets against VL.     

Anatomical characterization of Strobilanthes (Acanthaceae) species from the northern Western Ghats of India and its implication for identification at vegetative state

A comprehensive study of stem, leaf and petiole anatomy of 10 species of Strobilanthes from northern Western Ghats of India was carried out to identify characteristics which would enable species identification when flowering material is unavailable. In Strobilanthes, some species bloom annually, others are plietesials, i.e. they grow without blooming for several years and then produce huge quantities of flowers, release seeds and die. Therefore, alternative methods, such as anatomical characters, are essential to distinguish Strobilanthes species in their vegetative stage. We collected ten species of Strobilanthes for anatomical characterization. Under the bright‐field microscope, stem cross‐sections of different species were found to be undulate, quadrangular, quadrangular‐winged or terete. Study of the stem revealed a distinct outer and inner cortex, the distribution of cystoliths (CaCO₃ crystals), raphides (CaC₂H₂O₅ crystals) and sclereids which varied from species to species. Study of leaf anatomy showed structural variation and vascular bundle shapes that differed between the species. Leaf epidermal characters under light and scanning electron microscopy exhibited variation in characters such as stomatal index, stomatal length and width, stomatal type and presence of glandular and non‐glandular trichomes. The petiole anatomy was species‐specific, especially with respect to vascular bundle structure and the distribution of structures such as sclereids, cystoliths, sphaeraphides and tannin cells varied. Hence, unique anatomical features of the stem, leaf and petiole could be used as taxonomic characters to identify Strobilanthes species in a vegetative state.     

Annotated checklist of Senegalia and Vachellia (Fabaceae: Mimosoideae) for the Indian subcontinent

An annotated checklist of Senegalia Raf. and Vachellia Wight & Arn. taxa for the Indian subcontinent is presented, following the fragmentation and retypification of the former broadly defined genus Acacia Mill. The countries encompassed by this study include Bangladesh, Bhutan, India, Maldives, Nepal, Pakistan and Sri Lanka. All indigenous species (and a few introductions) in this region previously referred to Acacia belong to Senegalia and Vachellia. All Acacia s.s. taxa are introduced (principally from Australia) and are not included in the study. There are 22 species of Senegalia (21 indigenous, 1 introduced; representing 23 taxa) and 21 species of Vachellia (12 indigenous, 9 introduced; representing 27 taxa) currently recognized for the subcontinent. The largest country, India, has most species. This checklist complements that which was recently provided for these genera in southeast Asia and China. Two names formerly recorded for the Indian subcontinent are excluded, namely, Senegalia intsia (L.) Maslin is a nomen confusum and Acacia pennata subsp. hainanensis (Hayata) I. C. Nielsen is now known to be restricted to southern China and Vietnam. Acacia eriantha Desv. is an unresolved name. The following new combinations are made herein: Senegalia tanjorensis (Ragup., Thoth. & A.Mahad.) A.S.Deshpande & Maslin, Vachellia campbellii (Arn.) A.S.Deshp., & Maslin and V. pseudowightii (Thoth.) A.S.Deshpande & Maslin. A lectotype has been selected for Acacia pennata var. canescens Graham ex Kurz (= Senegalia pennata (L.) Maslin).     

Exploratory algorithm to devise multi-epitope subunit vaccine by investigating Leishmania donovani membrane proteins

Visceral leishmaniasis (VL) is a deadly parasitic infection which affects poorest to poor population living in the endemic countries. Increasing resistant to existing drugs, disease burden and a significant number of deaths, necessitates the need for an effective vaccine to prevent the VL infection. This study employed a combinatorial approach to develop a multi-epitope subunit vaccine by exploiting Leishmania donovani membrane proteins. Cytotoxic T- and helper T-lymphocyte binding epitopes along with suitable adjuvant and linkers were joined together in a sequential manner to design the subunit vaccine. The occurrence of B-cell and IFN-γ inducing epitopes approves the ability of subunit vaccine to develop humoral and cell-mediated immune response. Physiochemical parameters of vaccine protein were also assessed followed by homology modeling, model refinement and validation. Moreover, disulfide engineering was performed for the increasing stability of the designed vaccine and molecular dynamics simulation was performed for the comparative stability purposes and to conform the geometric conformations. Further, molecular docking and molecular dynamics simulation study of a mutated and non-mutated subunit vaccine against TLR-4 immune receptor were performed and respective complex stability was determined. In silico cloning ensures the expression of designed vaccine in pET28a(+) expression vector. This study offers a cost-effective and time-saving way to design a novel immunogenic vaccine that could be used to prevent VL infection.

Communicated by Ramaswamy H. Sarma