Insights into the dissociative ionization of glycine by PEPICO experiments.

The fragmentation of glycine (NH2CH2COOH) has been studied by photoelectron-photoion coincidence, PEPICO, experiments at 60 eV photon energy. Glycine practically fragments at the ionization threshold, with the charge being on the H2NCH2+ moiety, due to ejection of an electron from the nitrogen lone pair of the highest occupied molecular orbital. To observe the formation of the complementary cation COOH+ further energy is needed. The flexibility with respect to rotation about the C-C, C-N and C-O bonds makes glycine exist in the gas phase in several conformers of both Cs and C1 point group symmetry in the neutral as well as ion states. The ionization can lead to stabilization of some conformations, rearrangements and, last but not least, H migration between the two moieties. The results of these experiments prove the sensitivity of PEPICO to pin point all these processes.

Plasmon Energy Transfer Driven by Electrochemical Tuning of Methylene Blue on Single Gold Nanorods.

Plasmonic photocatalysis has attracted interest for its potential to generate energy-efficient reactions, but ultrafast internal conversion limits efficient plasmon-based chemistry. Resonance energy transfer (RET) to surface adsorbates offers a way to outcompete internal conversion pathways and also eliminate the need for sacrificial counter-reactions. Herein, we demonstrate RET between methylene blue (MB) and gold nanorods (AuNRs) using in situ single-particle spectroelectrochemistry. During electrochemically driven reversible redox reactions between MB and leucomethylene blue (LMB), we show that the homogeneous line width is broadened when spectral overlap between AuNR scattering and absorption of MB is maximized, indicating RET. Additionally, electrochemical oxidative oligomerization of MB allowed additional dipole coupling to generate RET at lower energies. Time-dependent density functional theory-based simulated absorption provided theoretical insight into the optical properties, as MB molecules were electrochemically oligomerized. Our findings show a mechanism for driving efficient plasmon-assisted processes by RET through the change in the chemical states of surface adsorbates.

Resveratrol's Hidden Hand: A Route to the Optical Detection of Biomolecular Binding.

Resveratrol is a stilbenoid phytoalexin with promising myriad health benefits predominantly contributed by the trans ( E) diastereomeric form. A recent study has implicated the cis ( Z) diastereomer in human health. This stereoisomer binds with high affinity to human tyrosyl-tRNA synthetase, initiating a downstream cascade that promotes the expression of genes associated with the cellular stress response. We discovered that the nonplanar structure of the cis-resveratrol conformer possesses certain chiral signals in its simulated vibrational circular dichroism (VCD) and Raman optical activity (ROA) spectra. These features may be used for the optical detection of the binding event and in understanding the more diversified biological roles of trans-resveratrol over cis-resveratrol. We use a density functional theory model, which is validated against the known results for the E diastereomer. The Z diastereomer is significantly nonplanar and can exist in two helical atropisomeric forms. These forms exchange rapidly in solution, but only one is observed to bind with the synthetase. This suggests that the binding may generate an enantiomeric excess, leading to detectable changes in the vibrational optical activity spectra. We identify candidate features at 998, 1649, and 1677 cm-1 in the ROA and at 1642 and 3834 cm-1 in the VCD spectra of Z-resveratrol that may be useful for this purpose.

Dominant Carbons in trans- and cis-Resveratrol Isomerization.

A comprehensive analysis for isomerization of geometric isomers in the case of resveratrol (R) has been presented. As an important red wine molecule, only one geometric isomer of resveratrol, i.e., trans-R rather than cis-R, is primarily associated with health benefit. In the present study, density function theory (DFT) provides accurate descriptions of isomerization of resveratrol. The nearly planar trans-R forms a relatively rigid and less flexible conjugate network, but the nonplanar cis-R favors a more flexible structure with steric through space interaction. The calculated carbon nuclear magnetic resonance (NMR) chemical shift indicates that all carbons are different in the isomers; it further reveals that four carbon sites, i.e., C(6), C(8)═C(9), and C(11), have a significant response to the geometric isomerization. Here C(6) is related to the steric effect in cis-R, whereas C(11) may indicate the isomerization proton transfer on C(9) linking with the resorcinol ring. The excess orbital energy spectrum (EOES) confirms the NMR "bridge of interest" carbons and reveals that five valence orbitals of 34a, 35a, 46a, 55a, and 60a respond to the isomerization most significantly. The highest occupied molecular orbital (HOMO), 60a, of the isomer pair is further studied using dual space analysis (DSA) for its orbital momentum distributions, which exhibit p-electron dominance for trans-R but hybridized sp-electron dominance for cis-R. Finally, energy decomposition analysis (EDA) highlights that trans-R is preferred over cis-R by -4.35 kcal·mol-1, due to small electrostatic energy enhancement of the attractive orbital energy with respect to the Pauli repulsive energy.

Molecular dynamics studies on the buffalo prion protein.

It was reported that buffalo is a low susceptibility species resisting to transmissible spongiform encephalopathies (TSEs) (same as rabbits, horses, and dogs). TSEs, also called prion diseases, are invariably fatal and highly infectious neurodegenerative diseases that affect a wide variety of species (except for rabbits, dogs, horses, and buffalo), manifesting as scrapie in sheep and goats; bovine spongiform encephalopathy (BSE or "mad-cow" disease) in cattle; chronic wasting disease in deer and elk; and Creutzfeldt-Jakob diseases, Gerstmann-Sträussler-Scheinker syndrome, fatal familial insomnia, and Kulu in humans etc. In molecular structures, these neurodegenerative diseases are caused by the conversion from a soluble normal cellular prion protein (PrP(C)), predominantly with α-helices, into insoluble abnormally folded infectious prions (PrP(Sc)), rich in ß-sheets. In this article, we studied the molecular structure and structural dynamics of buffalo PrP(C) (BufPrP(C)), in order to understand the reason why buffalo is resistant to prion diseases. We first did molecular modeling of a homology structure constructed by one mutation at residue 143 from the NMR structure of bovine and cattle PrP(124-227); immediately we found that for BufPrP(C)(124-227), there are five hydrogen bonds (HBs) at Asn143, but at this position, bovine/cattle do not have such HBs. Same as that of rabbits, dogs, or horses, our molecular dynamics studies also revealed there is a strong salt bridge (SB) ASP178-ARG164 (O-N) keeping the ß2-α2 loop linked in buffalo. We also found there is a very strong HB SER170-TYR218 linking this loop with the C-terminal end of α-helix H3. Other information, such as (i) there is a very strong SB HIS187-ARG156 (N-O) linking α-helices H2 and H1 (if mutation H187R is made at position 187, then the hydrophobic core of PrP(C) will be exposed (L.H. Zhong (2010). Exposure of hydrophobic core in human prion protein pathogenic mutant H187R. Journal of Biomolecular Structure and Dynamics 28(3), 355-361)), (ii) at D178, there is a HB Y169-D178 and a polar contact R164-D178 for BufPrP(C) instead of a polar contact Q168-D178 for bovine PrP(C) (C.J. Cheng, & V. Daggett. (2014). Molecular dynamics simulations capture the misfolding of the bovine prion protein at acidic pH. Biomolecules 4(1), 181-201), (iii) BufPrP(C) owns three 310 helices at 125-127, 152-156, and in the ß2-α2 loop, respectively, and (iv) in the ß2-α2 loop, there is a strong π-π stacking and a strong π-cation F175-Y169-R164.(N)NH2, has been discovered.

Use of natural molecules as anti-angiogenic inhibitors for vascular endothelial growth factor receptor.

Angiogenesis refers to the formation of new blood vessels, controlled by certain chemicals, which on stimulation repairs damaged cells or form new ones. Other chemicals, called angiogenesis inhibitors, signal the process to stop, having only mild side effects and are non toxic to most healthy cells. In our study, attempt was made to find potent anti-angiogenic inhibitor (pazopanib was considered as a reference drug) for vascular endothelial growth factor receptor (VEGFR-1/FLT-1), which served as a molecular target, using natural agents targeting biological processes important in cancer. Hundreds of natural molecules were initially screened based on lipinski's rule of five and the satisfying ones were taken for receptor-ligand interaction study using docking tools like HEX and quantum. Around fifteen molecules were taken as lead molecule and their binding pocket on VEGF was analyzed using SwissPDBviewer and Q-site finder. The investigational drug pazopanib was found to be interacting with leucine 32 and glutamine 30 in terms of hydrogen bond with the distance of 1.86 and 2.49 A0 respectively. Ames test for the molecules was predicted for probability of mutagenicity on molecular systems such as blood, cardiovascular system, gastrointestinal system; kidney, liver and lung were considered for further screening of the molecules. The natural molecules curcumin, epigallocatechin gallate (EGCG), barrigtozenol and finasteride were showing reliable interaction with VEGFR and their pharmacokinetics parameters were comparatively good than the pazopanib. The dietary product curcumin and EGCG can be cancer chemopreventive agents and the natural molecules barringtozenol and finasteride can be effective inhibitors for VEGFR.

Network properties of protein-decoy structures.

Convergence of the vast sequence space of proteins into a highly restricted fold/conformational space suggests a simple yet unique underlying mechanism of protein folding that has been the subject of much debate in the last several decades. One of the major challenges related to the understanding of protein folding or in silico protein structure prediction is the discrimination of non-native structures/decoys from the native structure. Applications of knowledge-based potentials to attain this goal have been extensively reported in the literature. Also, scoring functions based on accessible surface area and amino acid neighbourhood considerations were used in discriminating the decoys from native structures. In this article, we have explored the potential of protein structure network (PSN) parameters to validate the native proteins against a large number of decoy structures generated by diverse methods. We are guided by two principles: (a) the PSNs capture the local properties from a global perspective and (b) inclusion of non-covalent interactions, at all-atom level, including the side-chain atoms, in the network construction accommodates the sequence dependent features. Several network parameters such as the size of the largest cluster, community size, clustering coefficient are evaluated and scored on the basis of the rank of the native structures and the Z-scores. The network analysis of decoy structures highlights the importance of the global properties contributing to the uniqueness of native structures. The analysis also exhibits that the network parameters can be used as metrics to identify the native structures and filter out non-native structures/decoys in a large number of data-sets; thus also has a potential to be used in the protein 'structure prediction' problem.

Anti hyperglycaemic study of natural inhibitors for Insulin receptor.

UNLABELLED: Diabetes is a metabolic disorder associated with either improper functioning of the beta-cells or wherein cells fail to use insulin properly. Insulin, the principal hormone regulates uptake of glucose from the blood into most of the cells except central nervous system. Therefore, deficiency of insulin or the insensitivity of its receptors plays a key role in all forms of diabetes. In the present work, attempt has been made to find out plant sources which show anti hyperglycaemic activity (AhG) (i.e. compounds that bring down the blood glucose level in the body). Ayurvedic plants showing AhG activity formed the basis of our study by using the platform of Computer Aided Drug Designing (CADD). Among 600 plants showing AhG activity, 500 compounds were selected and screened, out of which 243 compounds showed drug likeness property that can be used as therapeutic ligand/drug. Initial screening of such compounds was done based on their drug likeness or biochemical properties. Dynamic interaction of these molecules was captured through Protein-Ligand study. It also gave an insight of the binding pockets involved. Bench marking of all the parameters were done using the diabetic inhibitor drug, Glipizide. Pharmacokinetic studies of the compounds such as Aloins, Capparisine, Funiculosin and Rhein exhibited less toxicity on various levels of the body. As a conclusion these ligands can lay a foundation for a better anti-diabetic therapy. ABBREVIATIONS: AhG - Anti hyperglycaemic, CADD - Computer Aided Drug Designing.

Bamboo-infoline: A database for North Bengal Bamboo's.

UNLABELLED: Bamboo, the "Green Gold", included in the non-timber forest products has both ecological and economic importance. Here is an attempt to describe a database named "Bambooinfoline" , which provides enumeration of the different species of bamboos found in North Bengal, with special emphasis on taxonomy, edible properties, chemical constituents, morphological features along with tissue culture specifications, which in turn benefits of scientific community. AVAILABILITY: The database is freely available at http://www.bamboodb.ind.in/