Molecular Dynamics Studies on the Buffalo Prion Protein

It was reported that buffalo is a low susceptibility species resisting to prion diseases, which are invariably fatal and highly infectious neurodegenerative diseases that affect a wide variety of species. In molecular structures, TSE neurodegenerative diseases are caused by the conversion from a soluble normal cellular prion protein, predominantly with alpha-helices, into insoluble abnormally folded infectious prions, rich in beta-sheets. This paper studies the molecular structure and structural dynamics of buffalo prion protein, in order to reveal the reason why buffalo are resistant to prion diseases. We first did molecular modeling of a homology structure constructed by one mutation at residue 143 from the Nuclear Magnetic Resonance structure of bovine and cattle PrP(124-227); immediately we found for buffalo PrPC(124-227) there are 5 hydrogen bonds at Asn143, but at this position bovine/cattle do not have such hydrogen bonds. Same as that of rabbits, dogs or horses, our molecular dynamics studies also confirmed there is a strong salt bridge ASP178-ARG164 (O-N) keeping the beta2-alpha2 loop linked in buffalo. We also found there is a very strong hydrogen bond SER170-TYR218 linking this loop with the C-terminal end of alpha-helix H3. Other information such as (i) there is a very strong salt bridge HIS187-ARG156 (N-O) linking alpha-helices H2 and H1 (if mutation H187R is made at position 187 then the hydrophobic core of PrPC will be exposed), (ii) at D178, there is a hydrogen bond Y169-D178 and a polar contact R164-D178 for BufPrPC instead of a polar contact Q168-D178 for bovine PrPC, (iii) BufPrPC owns 3-10 helices at 125-127, 152-156 and in the beta2-alpha2 loop respectively, and (iv) in beta2-alpha2 loop there are strong pi-contacts, etc, has been discovered

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

How similar Is the electronic structures of β–lactam and alanine?

The C1s spectra of β-lactam i.e. 2-azetidinone (C3H5NO), a drug and l-alanine (C3H7NO2), an amino acid, exhibit striking similarities, which may be responsible for the competition between 2-azetidinone and the alanyl-alanine moiety in biochemistry. The present study is to reveal the degree of similarities and differences between their electronic structures of the two model molecular pairs. It is found that the similarities in C1s and inner valence binding energy spectra are due to their bonding connections but other properties such as ring structure (in 2-azetidinone) and chiral carbon (alanine) can be very different. Further, the inner valence region of ionization potential greater than 18 eV for 2-azetidinone and alanine is also significantly similar. Finally the strained lactam ring exhibits more chemical reactivity measured at all non-hydrogen atoms by Fukui functions with respect to alanine

Dominant Carbons in <i>trans</i>- and <i>cis</i>-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., <i>trans</i>-R rather than <i>cis</i>-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 <i>trans</i>-R forms a relatively rigid and less flexible conjugate network, but the nonplanar <i>cis</i>-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 <i>cis</i>-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 34<i>a</i>, 35<i>a</i>, 46<i>a</i>, 55<i>a</i>, and 60<i>a</i> respond to the isomerization most significantly. The highest occupied molecular orbital (HOMO), 60<i>a</i>, of the isomer pair is further studied using dual space analysis (DSA) for its orbital momentum distributions, which exhibit p-electron dominance for <i>trans</i>-R but hybridized sp-electron dominance for <i>cis</i>-R. Finally, energy decomposition analysis (EDA) highlights that <i>trans</i>-R is preferred over <i>cis</i>-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

Electro-optical response of the combination of two twisted nematic liquid crystal cells in series and the applicability of the extended Jones matrix

A typical electro-optical response is observed by connecting two twisted nematic liquid crystal cells in series and placed back to back such that the director orientation on the back glass substrate of the first cell coincides with the director orientation of the front glass substrate of the second cell and vice versa. The two cells connected in series show cholesteric rotation. It is observed that for a given frequency the output transmittance oscillates having distinct maxima and minima with varying voltage and no flickering of transmittance have been observed at low frequencies. Variation of transmittance with frequency for given voltages is also reported and it has been found that increase of voltage at high frequency does not alter the transmittance appreciably. A discussion on the extended Jones matrix formulation and the scope of its applicability for this case is also given

Dielectric relaxation and ac conductivity behaviour of polyvinyl alcohol-HgSe quantum dot hybrid films

Here we report a comparative study on the dielectric relaxation and ac conductivity behaviour of pure polyvinyl alcohol (PVA) and PVA-mercury selenide (HgSe) quantum dot hybrid films in the temperature range 298K <= T <= 420K and in the frequency range 100 Hz <= f <= 1 MHz. The prepared nanocomposite exhibits a larger dielectric constant as compared to the pure PVA. The real and imaginary parts of the dielectric constants were found to fit appreciably with the modified Cole-Cole equation, from which temperature-dependent values of the relaxation times, free charge carrier conductivity and space charge carrier conductivity were calculated. The relaxation time decreases with the quantum dot's inclusion in the PVA matrix and with an increase in temperature, whereas free charge carrier conductivity and space charge carrier conductivity increases with an increase in temperature. An increase in ac conductivity for the nanocomposites has also been observed, while the charge transport mechanism was found to follow the correlated barrier hopping model in both cases. An easy-path model with a suitable electrical equivalent circuit has been employed to analyse the temperature-dependent impedance spectra. The imaginary part of the complex electric modulus spectra exhibit an asymmetric nature and a non-Debye type of behaviour, which has been elucidated considering a generalized susceptibility function. The electric modulus spectra of the nanocomposite demonstrate a smaller amplitude and broader width, as compared to the pure PVA sample

Structural characterization and observation of variable range hopping conduction mechanism at high temperature in CdSe quantum dot solids

We have used Rietveld refinement technique to extract the microstructural parameters of thioglycolic acid capped CdSe quantum dots. The quantum dot formation and its efficient capping are further confirmed by HR-TEM, UV-visible and FT-IR spectroscopy. Comparative study of the variation of dc conductivity with temperature (298K <= T <= 460 K) is given considering Arrhenius formalism, small polaron hopping and Schnakenberg model. We observe that only Schnakenberg model provides good fit to the non-linear region of the variation of dc conductivity with temperature. Experimental variation of ac conductivity and dielectric parameters with temperature (298K <= T <= 460 K) and frequency (80 Hz <= f <= 2MHz) are discussed in the light of hopping theory and quantum confinement effect. We have elucidated the observed non-linearity in the I-V curves (measured within +/-50 V), at dark and at ambient light, in view of tunneling mechanism. Tunnel exponents and non-linearity weight factors have also been evaluated in this regard. (C) 2013 American Institute of Physics. [http://dx.doi.org/10.1063/1.4794019

Preparation and introduction of CdSe quantum dots in a 5CB twisted nematic liquid crystal cell: Observation of ordered array of nanostructures

Thioglycolic acid capped cadmium selenide (CdSe) quantum dots have been prepared by chemical synthesis method. HR-TEM and SAED characterization confirm the formation of CdSe quantum dots with approximate particle size of 3.8 nm which is also comparable to the crystallite size as determined from the XRD analysis. This II-VI semiconductor quantum dot is introduced in a positive dielectric anisotropic liquid crystal host and then injected into a twisted nematic liquid crystal cell where the dots agglomerates and sports ordered arrays. Effect of the application of dc voltage on the composite system is also observed with an optical polarizing microscope