Uncovering allostery and regulation in SORCIN through molecular dynamics simulations.

Soluble resistance-related calcium-binding protein or Sorcin is an allosteric, calcium-binding Penta-EF hand (PEF) family protein implicated in multi-drug resistant cancers. Sorcin is known to bind chemotherapeutic molecules such as Doxorubicin. This study uses in-silico molecular dynamics simulations to explore the dynamics and allosteric behavior of Sorcin in the context of Ca2+ uptake and Doxorubicin binding. The results show that Ca2+ binding induces large, but reversible conformational changes in the Sorcin structure which manifest as rigid body reorientations that preserve the local secondary structure. A reciprocal allosteric handshake centered around the EF5 hand is found to be key in Sorcin dimer formation and stabilization. Binding of Doxorubicin results in rearrangement of allosteric communities which disrupts long-range allosteric information transfer from the N-terminal domain to the middle lobe. However, this binding does not result in secondary structure destabilization. Sorcin does not appear to have a distinct Ca2+ activated mode of Doxorubicin binding.Communicated by Ramaswamy H. Sarma.

Theoretical insights on the development of a 55-77 graphene sheet by embedding Agn=1-4 and Pdn=1-4 metal nanoclusters for efficient CO2 capture.

Recent advancements in two-dimensional (2D) allotropes of carbon materials and their usage as superior CO2 adsorbents can decrease the detrimental impact of CO2 on climate change. With the use of quantum chemical calculations, the effect of metal clusters (Agn = 1-4 and Pdn = 1-4) on the structural and electrical characteristics of 55-77 2D graphene sheet is examined in the current work with an aim towards enhancing CO2 capture capacity. The findings revealed that the binding energy (Eb) of the 55-77 sheet decoration with Pdn = 1-4 metal clusters are greater owing to chemisorption by 1.17 eV, 1.69 eV, 0.27 eV, and 1.58 eV than the decoration with Agn = 1-4 clusters. Moreover, CO2 molecules adsorb on the Pdn = 1-4 cluster decorated systems having -0.35 eV, 0.83 eV, 1.53 eV, and -0.98 eV greater adsorption energies than on the Agn = 1-4 decorated 55-77 sheet due to a stronger charge transfer. Further, the findings of an atoms in molecules (AIM) study show that the interaction between CO2 and Pdn = 1-4 decorated 55-77 sheet is partially covalent and non-covalent, confirming the greater charge transfer between the CO2 molecule and Pdn = 1-4 decorated 55-77 systems. Moreover, the CO2 adsorption on Pdn = 1-4 decorated 55-77 systems is clearly demonstrated by non-covalent interaction (NCI) analysis to be a strong electrostatic interaction at sign(λ2)ρ = -0.05 a.u, and this is further supported by an electron localization function (ELF) map. The highest CO2 adsorption capacity is obtained for 55-77/Pd1+CO2 with the value of 6.27 wt % which concludes 55-77 sheet with Pdn decoration is a more suitable structure for CO2 adsorption than the Agn decorated system.

Epigenetically modified nucleobases (5hmc, 5fc, and 5caC) interaction with boron and nitrogen doped porous graphene (B/N-pGr) as promising materials for biosensing application: A density functional theory calculations.

In this present work, porous graphene (pGr), boron (B-pGr), and nitrogen (N-pGr) doped porous sheets are explored as a bio-sensor device for sensing modified nucleobases (MBs) in cancer therapy using density functional theory (DFT). The obtained geometrical, energetic and electronic properties revealed that the B-pGr is highly reactive and it adsorbs MBs better than the pGr and N-pGr, because B atom holds empty p-orbitals which easily interact with partially filled p-orbital of N and O atom. Thus, the adsorption energies of 5hmc, 5caC, and 5fc on B-pGr are high rather than the pGr and N-pGr. The corresponding adsorption energies are -96.074, -77.0, and -60.721 kcal/mol for 5hmc, 5caC, and 5fc respectively. The positive signature of ΔN values (0.005 eV, 0.076 eV, and 0.047 in MBs on pGr and 0.171 eV, 0.252 eV and 0.205 eV in MBs on N-pGr) are obtained at MBs on pGr and N-pGr complex. The negative ΔN values (-0.141 eV, -0.032 eV, and -0.061 eV in MBs on B-pGr) are obtained at MBs of B-pGr. The calculated absorption values shows that the B-pGr is strongly adsorbed MBs at 342 nm. The obtained results exhibit that the B-pGr sheet retains significant therapeutic potential as a bio-sensing application for cancer therapy.

Kinetics and degradation of camphene with OH radicals and its subsequent fate under the atmospheric O2 and NO radicals - A theoretical study.

Camphene (C10H16) is an abundant bicyclic monoterpene in the atmosphere which can be easily oxidized by the atmospheric OH radicals. In this study, the oxidation of camphene with OH radicals and its subsequent reactions are studied using quantum chemical method. Thermochemical parameters show that the addition of OH radicals to the terminal C10 atom of camphene is thermodynamically more stable than the addition of OH radicals to the internal C7 atom of camphene. The reaction force profile demonstrates that the formation of two hydroxyalkoxy radical intermediates (I1a and I2a) are mainly dominated by the structural rearrangement with 94.28% and 99.43% of the total energy, respectively. The overall reaction rate coefficient for camphene + OH radical is 2.1⨯10-12 cm3 molecule-1 sec-1 at 298 K and 1 atm which agree well with the experimental reaction rate coefficient (5.58⨯10-11 cm3 molecule-1 sec-1) for the reaction of camphene with OH radical. The branching ratio for the addition of OH radical to the C10 position of camphene is 68.32%, and the C7 position of camphene is 31.68% at 298 K. The calculated lifetime reveals that camphene degrades quickly in the atmosphere owing to its short lifetime of 5.3 h. The obtained mechanistic and kinetic results reveal that the addition of OH radical to the C10 position is more dominant than the C7 position, and it is more stable and spontaneous in the atmosphere.

Exploring two-dimensional graphene and boron-nitride as potential nanocarriers for cytarabine and clofarabine anti-cancer drugs.

Development in two-dimensional (2D) drug-delivery materials have quickly translated into biological and pharmacological fields. In this present work, pristine graphene (PG) and hexagonal boron nitride (h-BN) sheets are explored as a drug carrier for cytarabine (CYT) and clofarabine (CLF) anti-cancer drugs using density functional theory (DFT). The obtained geometrical, energetic and electronic properties revealed that the PG sheet is more reactive and it adsorbs CYT and CLF anti-cancer drugs better than the h-BN sheet. The adsorption energies of CYT and CLF on PG sheet is -24.293 and -23.308 kcal/mol respectively, this is due to the delocalized electrons present in the PG sheet. The flow of electron direction between anti-cancer drugs and 2D sheet are calculated by ΔN, ΔEA(B), and ΔEB(A) parameters and Natural bond orbital analysis (NBO). The electronic and optical properties are calculated to understand the chemical reactivity and stability of the complex systems. The obtained results exhibit that the PG sheet retains significant therapeutic potential as a drug delivery vehicle for a drug molecule to treat cancer therapy.

Exploring the nature of interaction and stability between DNA/RNA base pairs and defective & defect-dopant graphene sheets. A possible insights on DNA/RNA sequencing.

A quantum chemical investigation is performed to understand the adsorption behaviour of DNA/RNA base pairs onto the defective (Di-Vacancy (DV) and Stone-Wales (SW)), boron (B) and silicon (Si) defect-dopant graphene (B-DV, Si-DV, B-SW, and Si-SW) sheets using density functional theory (DFT). The stability of DNA/RNA base pairs on the Si-SW sheet is found to be -80.59 kcal/mol (G-C), -70.21 kcal/mol (A-T), and -69.78 kcal/mol (A-U). The quantum theory of atoms in molecule (QTAIM) analysis concluded that the interaction of DNA/RNA base pair on Si-SW sheet has partially electrostatic and partially covalent (Si⋯N) characters. The natural bond orbital analysis (NBO), electron density difference map (EDDM), and natural population analysis (NPA) are revealed that the charge has been transferred from DNA/RNA base pair to defective and defective-dopant graphene sheet. From the time-dependent density functional theory (TD-DFT), a strong redshift is observed at 482 nm for GC-Si-SW, 494 nm for AT-Si-SW, and 497 nm for AU-Si-SW. Hence, the substantial variations in the HOMO-LUMO gap (∆EHL) and UV spectra of Si-SW sheet after the adsorption of DNA/RNA base pair can be beneficially exploited to design a new bio-sensor or DNA/RNA sequencing devices.

Modeling of Si-B-N Sheets and Derivatives as a Potential Sorbent Material for the Adsorption of Li+ Ion and CO2 Gas Molecule.

In the present exploration, a few Si-B-N derivatives are derived to adsorb Li ions and CO2 gas molecules for the potential application of metal-air batteries. The newly derived structure's bond lengths are as follows: Si=Si, 2.2 Å; Si-B, 1.9 Å; Si-N, 1.7 Å; and B-N, 1.4 Å, consistent with the experimental results of relevant structures. The stability of the newly derived structures is examined by the atom-centered density propagation study by varying the temperature from 270 to 400 K, and no structural variations are observed throughout the dynamics. Li adsorption on the Si4B2 ring has the maximum binding energy of -3.9 eV, and the result is consistent with the previous results. The rings with the 2:1 silicon-boron ratio provide strong adsorption for Li atoms. The calculated maximum electromotive force of the newly derived sheets is 0.56 V with the maximum theoretical density of 783 Wh/kg. Similarly, the maximum adsorption of CO2 on the sheet is -0.106 eV, which is considerably higher than that on graphene and its derivatives. CO2 adsorption has been carried out in the presence of water molecules to investigate the change in CO2 adsorption with the moisture (water) content, and the results show no significant change in the adsorption of CO2 with moisture. However, water has a strong interaction with the maximum interaction energy of -0.72 eV. Further, to explore the potential ability of the sheets, each sheet's edges are examined as hydrogen storage expedient and the surface as an artificial photosynthesis platform. The Si4B2 ring is more favorable for the adsorption of H atom with the chemisorption of -7.138 eV. Similarly, all of the major UV-absorption spectral peaks fall between 450 and 800 nm, which shows that the sheet can be used as an artificial photosynthesis platform.