Journal of Computational Biophysics and Chemistry

Nonlinear optical (NLO) materials have attracted bounteous scientific attention in the modern era because of their optoelectronic and biological applications. In this respect, an attempt is made to present thermodynamically stable superalkali metals (Li₃N, Li₃O, Li₃S and Li₃F)-doped sumanene (C${}_{21}$H${}_{12}$)-based complexes with fine NLO response properties. Nine isomers (I–III of Li₃N@Sumanene, I–II of Li₃O@Sumanene, I–II of Li₃S@Sumanene and I–II of Li₃F@Sumanene) are proposed, and their geometric, thermodynamic, electronic and NLO properties are explored by using density functional theory (DFT) calculations. Computational results reveal that the $E_{H-L}$ gap is reduced up to 0.56eV for doped complexes. The maximum hyperpolarizability response is calculated $1.084\times 10^5$a.u. for isomer II of the Li₃F@Sumanene series. The participation of distinct fragments, type of interaction, and charge transfer are computed by the corresponding TDOS and PDOS, NCI and NBO analysis. For UV–Vis analysis and crucial excitation state, TD-DFT calculations are carried out, which exhibits that all doped complexes are transparent in the UV region. NCI analysis confirmed the Van-der Waals interactions as an important mode of adsorption between superalkalis and sumanene. This report provides an efficient superalkali doping technique for creating highly effective future NLO systems and recommends superalkali-doped sumanene systems as ideal NLO prospects for future NLO applications.

In this study we analyzed the sequence and structure of the human DISC1-Ndel1 complex using bioinformatics tools and molecular dynamics simulation studies. Multiple sequence alignment between the homologue protein sequences in primates shows that corresponding positions of residues in Ndel1 are highly conserved, while the DISC1 has variable conservation lines demonstrating its tolerability against various mutations during evolutionary time scale. In comparison with the mouse variant, structural analysis has shown that the evolutionary inserted charged residues in the human DISC1 (E${}^{837}$-R${}^{838}$) can establish intra-chain electrostatic interactions with the K${}^{819}$-E${}^{820}$ dipeptide that may result in more stability of the DISC1 chain. According to MD simulation studies, the compactness for the human variant of the DISC1-Ndel1 is considerably lower than that of the mouse variant. Analysis of structural fluctuation shows that a fragment at the N-terminus side of the human DISC1 has more residual fluctuation. However, the Ndel1 chain of the human variant has globally more flexibility compared with the mouse variant. Considering the identical amino acid sequence of the Ndel1 chains of human and mouse, it concluded that there is a competition between the inter-chain and intra-chain electrostatic interaction in the human DISC1 that directs the complex to weaker inter-chain interactions with the expense of strengthening the intra-chain stabilizing interaction in complex.

In this study, geometries, electronic structure and first hyperpolarizability of metals doped 15-crown-5 (C5M) were explored through the density functional theory (DFT) method. Alkali metals (Li, Na, K) and silver (Ag) were placed inside and outside of the crown ether, respectively, to deliver three compounds designated as Li[C5M]Ag, Na[C5M]Ag and K[C5M]Ag. All designed complexes were optimized at singlet, triplet, quintet and septet states, where the singlet state was identified as the stable state. The influence of doping on C5M can be investigated by energy gap fluctuation and it was noted that the smallest energy gap (4.68eV) was exhibited by K[C5M]Ag among all the intentional complexes, in contrast to reference C5M (12.73eV). Moreover, the density of state (DOS), transition density matrix (TDM), noncovalent interaction (NCI), molecular electrostatic potential (MESP) and electron density distribution map (EDDM) analysis were implemented. Static isotropic polarizability values were observed in the range of $17.15\times 10^{-24}$–$34.68\times 10^{-24}$ esu which were comparable to dynamic isotropic polarizability values; $17.18\times 10^{-24}$–$35.40\times 10^{-24}$. Li[C5M]Ag revealed maximum first hyperpolarizability ($\beta$) of $45.96\times 10^{-30}$esu with the minimum transition energy ($\mathrm{\Delta }E$) of 2.93eV.

The S_N2 and proton transfer (PT) pathways for ${\mathrm{\text{OH}}}^{-}+{\mathrm{\text{NH}}}_2$Cl reaction are represented by employing various electronic structure computations. Both back-side S_N2 and PT channels are exothermic and stationary points of PESs are below the reactant asymptote. Overall, the PES is similar to the C-centered S_N2 reactions. Conversely, ion-dipole complex was not found for ${\mathrm{\text{OH}}}^{-}+{\mathrm{\text{NH}}}_2$Cl system. The N–HOH/NH–Cl hydrogen bond characterizes on either side of the reaction barrier of nitrogen complexes. Moreover, a halogen-bonded complex (HO⁻–ClNH₂) and two types of H-bond complexes (HONH₂–Cl⁻ and Cl⁻–HONH₂) were described, predicting an important role in dynamics. The PT pathway may be the major channel in the title system, which is contradictory to ${\mathrm{\text{OH}}}^{-}+{\mathrm{\text{CH}}}_3$Cl and ${\mathrm{\text{F}}}^{-}+{\mathrm{\text{NH}}}_2$Cl reactions. Here, MP2, B3LYP and CAM-B3LYP methods show overall excellent consistency with CCSD(T)/CBS energies and are recommended to carry out dynamics simulations.

The Hsp90 family has been extensively studied as a promising target against cancer and neurodegenerative diseases due to its crucial role in protein maturation and transport. However, the toxic and side effects such as cardiotoxicity and ocular toxicity caused by the pan-inhibition of Hsp90 cannot be ignored. The development of highly selective inhibitors toward Hsp90$\alpha$ over Grp94 has been proved to be a feasible approach to avoid these toxic and side effects. Therefore, to explore the different binding modes of inhibitors against Hsp90$\alpha$ and Grp94, hybrid computational methods were used to demonstrate the interaction mechanism between selective inhibitors targeting Hsp90$\alpha$ and Grp94. The results showed that hydrogen bond interaction and hydrophobicity are crucial for the selective inhibition of Hsp90$\alpha$, while Grp94 specificity mainly relies on a typical hydrophobic cavity. These findings would provide the theoretical basis for the future development of novel selective inhibitors of Hsp90$\alpha$ and Grp94.

In this paper, we report results of using molecular modeling to assign specific Zn(II) binding affinities to the known binding sites of the YiiP–zinc transporter. YiiP is a cation-diffusion facilitator. It facilitates the transmembrane exchange of Zn(II) ions and protons. The crystal structure of this protein is known. There are several zinc binding sites, and some of the Zn(II) binding affinities have been measured, but the value of all the binding/dissociation constants and the exact assignment of the sites with these affinities are not completely understood. We have recently developed a fast and accurate coarse-grain framework for predicting protein pKa shifts named PKA17. In this paper, we report extending of the same technique to produce a methodology capable of quickly predicting metal–protein binding affinities. The new software has been named M21. It has been tested on several zinc–protein binding cases, and the average unsigned error in the binding energies has been found to be 2.17kcal/mol vs. the AMBER average error of 3.49kcal/mol ($K_d$ ratio of ca. 30 vs. the AMBER one of 330). We have then applied the M21 methodology to calculate and assign the YiiP–Zn(II) binding constants of $-$2.31$-$13.28kcal/mol ($K_d$ values from $2.04\times 10^{-2}$ to $1.85\times 10^{-10}$). We have also undertaken additional modifications of parameters. On one hand, we have included another 11 zinc binding proteins in our target fitting set. These were the Uno Ferro single chain (UFsc) and its modifications created by the Professor Olga Makhlynets group. On the other hand, we have significantly reduced the number of fittable parameters in order to further reduce the possibility of overfitting and to demonstrate the stability of the technique. The final parameter set has only eight adjustable parameters (as opposed to the above case with 17 independent parameters). The average error for the binding cases compared with the same AMBER test set as above did not change much and was still very low at 2.17kcal/mol. We believe that these results not only further validate the presented methodology but also point out a promising direction for potential multiple joint experimental and computational collaborative projects. Both PKA17 and M21 software have been deployed with web-based interfaces at http://kaminski.wpi.edu/PKA17/pka_calc.html and http://kaminski.wpi.edu/METAL/metal_calc.html, respectively.

Four metal-free carbazole-based acceptor-tuned organic molecules (denoted as CBa1–CBa4) based on electron-donor, $\pi$-spacer and electron-acceptor (D-$\pi$-A) for dye-sensitized solar cells (DSSCs) have been newly designed. The electronic structures, optical absorption ultraviolet-visible (UV–Vis) properties and photovoltaic (PV) parameters of CBa1–CBa4 dyes were computationally studied by the density functional theory (DFT) and time-dependent density functional theory (TDDFT) methods. These molecules were planned through chemical alterations of the acceptor group of a literature-based organic dye known as CB1 dye. The planning of CBa1–CBa4 dyes was to decrease the highest occupied molecular orbitals (HOMOs) and lowest unoccupied MOs (LUMOs) of the energy gap ($E_g$) and to red-shift their UV–Vis response compared to CB1. This study was initially performed using the exchange correctional (XC) and long-range corrected (LC) with the computational ideal in the TD-DFT method significantly to get an accurate absorption wavelength for CB1. From the XC and LC results, CAM-B3LYP functional is better matched with CB1. So, further newly organic CBa1–CBa4 dyes UV–Vis spectra were followed by this method. According to DFT and TDDFT results, CBa1 and CBa2 molecules were found to have reduced HOMOs–LUMOs energy gap, longer UV–Vis spectra and faster charger transfer (CT) character compared to CB1. The conclusion recommends that the newly designed molecules are hopeful and appropriate for optoelectronic devices. Hence, the work predicts to support the new scheming carbazole-based molecules with the studied properties for synthetizing to DSSC applications.

In this paper, newly metal-free four donor-$\pi$-acceptor (D-$\pi$-A) molecules (C1D1–C1D4) were designed and used for dye-sensitized solar cells (DSSCs) application, based on literature C1-1. Tetrahydroquinoline, thiophene, and 2-cyanoacrylic acid act as the electron-D, spacer, and electron-A/anchoring groups for all dyes, respectively, while the donor part was tuned and the effect was examined. The density functional theory (DFT) and time-dependent DFT (TD-DFT) have been used on the electronic transitions, geometric structures, absorption properties, electron injection ($\mathrm{\Delta }{G}_{\mathrm{\text{inject}}}$), dye regeneration ($\mathrm{\Delta }{G}_{\mathrm{\text{reg}}}$), light harvesting efficiency (LHE), ground and excited states of dipole moments (${\mu }_{\mathrm{\text{normal}}}$), open-circuit photovoltage ($e{V}_{\mathrm{\text{OC}}}$), molecular electrostatic potential (MEP) and Mulliken population analysis (MPA) of the dyes. The TD-DFT method using different functionals with exchange-correlational (XC) and long-range correlated (LC) was calculated to obtain literature data. The computational outcomes have displayed that the Coulomb-attenuating method (CAM-B3LYP) in conjunction with a 6-31G(d,p) basis set was proficient in calculating the UV-Vis spectra of the molecules. The frontier molecular orbitals’ (FMOs) contribution of the HOMOs and LUMOs of C1D1-C1D4 molecules can be confirming positive consequences on the regeneration and electron injection processes. In particular, C1D4 (N(CH3)₂) molecule shows a smaller energy gap ($E_g$), longer wavelength, high ${\mu }_{\mathrm{\text{normal}}}$ and $e{V}_{\mathrm{\text{OC}}}$. To conclude, these outcomes display that the calculated C1D1–C1D4 molecules are capable applicants to deliver better performance of the DSSCs.