Modeling Binding Studies Research Articles

Discovery of TRD‐93 as a novel DRAK2 inhibitor

AbstractDeath‐associated protein kinase‐related apoptosis‐inducing protein kinase 2 (DRAK2) has become a promising target for drug development. In search of novel and selective DRAK2 inhibitor motif, in vitro screen kinase assay was established performed using in‐house chemical libraries. After through hit triage procedure, N2‐(3,5‐dichlorophenyl)‐5‐fluoro‐N4‐methylpyrimidine‐2,4‐diamine (1) was selected as initial hit with structural novelty and drug‐likeness. During hit validation, structure–activity relationship of 1 was thoroughly disclosed and TRD‐93 was finally validated as hit for DRAK2 inhibition. TRD‐93 is small (mw = 290) but selectively potent to DRAK2 (IC50 = 0.16 μM) over other kinases including DAPK family kinases. Molecular binding model study of TRD‐93 to DRAK2 is also discussed.

Why ultrafast charge separation occurs in bulk-heterojunction organic solar cells: a multichain tight binding model study.

Bulk-heterojunction (BHJ) organic solar cells (OSCs) exhibit ultrafast charge separation (UCS) which enables lower geminate charge recombination and high internal quantum efficiency. Unravelling why UCS occurs in BHJ-OSCs is important for the exploration of devices in future, however it is still far from clear. In this work, we build a multichain tight-binding model to study the conditions for realizing UCS. We propose that two conditions are important: (i) the BHJ-OSC has a morphology with donor and acceptor molecules being individually aggregated; (ii) the ratio of the donor/acceptor interfacial coupling to the internal donor/donor and acceptor/acceptor coupling should be smaller than a threshold. In addition, we suggest that increasing the donor/acceptor energetic offset will boost the UCS efficiency. As a fundamental theoretical analysis on the underlying mechanism of UCS, our work provides design rules for optimizing high-performance BHJ OSCs.

Charge transfer and hybridization effect at the graphene-nickel interface: A tight binding model study

We have investigated here, the electronic and magnetic properties of graphene–nickel system by tight-binding mean-field approach. Strong hybridization between the 2pz orbital of graphene and 3dz2 orbital of nickel occurs when monolayer graphene is placed over a single layer of ferromagnetically ordered Ni (111) metal due to the excellent lattice matching between the two layers. This hybridization greatly affects the electronic and magnetic properties of the bilayer system, resulting in a significantly reduced local magnetic moment of the nickel layer and an enhanced induced spin polarization on the graphene layer. The calculated Hamiltonian revealed critical information regarding the first-, second-and third-nearest-neighbour hopping integrals of π− electrons of graphene besides the Coulomb correlation of electrons in nickel (111). The Hubbard type Coulomb interactions present in nickel lattices were treated within the mean-field approximation. Zubarev's technique was employed to calculate electronic Green's functions and subsequent investigation of the temperature dependent ferromagnetic magnetization of nickel (111)was carried out through self-consistent calculation. Further calculations regarding the induced magnetization in the graphene, total magnetization in bilayer layer system, electronic band dispersion, spin resolved density of states (DOS) and spin polarization efficiency have been carried out. The results were corroborated by experimental observations.

The Tight-Binding Study of the Temperature Dependent Anti-Ferromagnetic Order in Graphene

We propose a tight binding model study for graphene taking the electron hopping up to third-nearest-neighbors. The graphene placed on different polarized substrates introduces in-equivalences in the two sub-lattices of honeycomb unit cell of graphene. Further the electron/hole doping in graphene enhances the in-equivalence in both the sub-lattices. The Hubbard type Coulomb interaction between the electrons in both sub-lattices generates anti-ferromagnetic (AFM) order in graphene under certain conditions. Zubarev’s Green’s functions method is applied to solve the Hamiltonian. The spins of the electron in the two sub-lattices are assumed to be oriented in opposite directions giving rise to AFM order in the system. The magnetization is calculated from the Green’s functions and computed self-consistently. The effect of the presence of substrates and doping concentrations on magnetization is reported here.

Theory of dielectric loss in Graphene-on-substrate: A tight- binding model study

Graphene-on-substrate exhibits interesting dielectric behaviour due to screening of coulomb interaction induced by many body effects. In this communication we attempt to study the dielectric loss property of graphene within tight-binding model approach. The Hamiltonian consisting of electron hopping upto third-nearest-neighbour's with impurities in two in equivalent sub-lattices. The graphene-on-substrate raises the energy +Δ at one sub lattice and reduces energy -Δ at other sub lattice. Further we introduced coulomb interaction between π - electrons at the two sub lattices separately with the same effective coulomb interaction. We calculate polarization function Π(q, ω) which is a two particle Green's function arising due to charge-charge correlation by using Zubarev's Green's function technique. Finally we calculate dielectric function of graphene i.e. ε(q, ω) =1+Π(q,ω) at arbitrary wave vector q and frequency ra. The dielectric loss in graphene calculated from the imaginary part of dielectric function which is a measure of absorption spectrum. Only a few Fragmentary theoretical attempts have been made to utilize the full frequency and wave vector dependent dielectric function. We compute numerically the frequency dependent dielectric loss function for 100x100 momentum grid points. We observe a low energy Plasmon resonance peak and a high energy flat peak arising due to absorption of optical energy at substrate induced gap. With increase of small Plasmon wave vector, both low and high energy peaks approach each other. The dielectric loss at low energies exhibits a parabolic curve, but it exhibit a clear peak on introduction of higher order electron hopping's. The Coulomb interaction suppresses induced gap in graphene and decreases the optical energy absorption spectra. The increase of substrate induced gap shifts the high energy flat peak to higher energies and enhances the dielectric loss throughout the frequency range. Finally the effect of doping on dielectric loss is investigated and compared with the experimental results.

The Six Zinc Fingers of Metal-responsive Element Binding Transcription Factor-1 Form Stable and Quasi-ordered Structures with Relatively Small Differences in Zinc Affinities

Six Cys(2)His(2) zinc fingers (F1-6) comprise the DNA binding domain of metal-responsive element binding transcription factor-1 (MTF-1). F1-6 is necessary for basal and zinc-induced expression of metallothionein genes. Analysis of NMR structural and dynamic data for an F1-6 protein construct demonstrates that each zinc finger adopts a stable betabetaalpha fold in the presence of stoichiometric Zn(II), provided that all cysteine ligands are in a reduced state. Parallel studies of protein constructs spanning the four N-terminal core DNA binding fingers (F1-4) and two C-terminal low DNA affinity fingers (F5-6) reveal similar stable zinc finger structures. In both the F1-6 and F5-6 proteins, the finger 5 cysteines were found to readily oxidize at neutral pH. Detailed spectral density and hydrodynamic analysis of (15)N relaxation data revealed quasi-ordered anisotropic rotational diffusion properties of the six F1-6 zinc fingers that could influence MTF-1 DNA binding function. A more general effect on the rotational diffusion properties of Cys(2)His(2) zinc fingers was also uncovered that is dependent upon the position of each finger within multifinger domains. Analysis of NMR (1)H-(15)N-heteronuclear single quantum coherence spectral peak intensities measured as a function of added Zn(II) in conjunction with Zn(II) binding modeling studies indicated that the Zn(II) affinities of all MTF-1 zinc fingers are within approximately 10-50-fold. These analyses further suggested that metal sensing by MTF-1 in eukaryotic cells involves multiple zinc fingers and occurs over a 100-fold or less range of accessible Zn(II) concentration.

Intrinsic asymmetries in spin-valves: a tight binding model study

We have calculated the I– V curves, dynamical conductance, and tunneling magnetoresistance (TMR) of 1D magnetic tunneling junction through singleband tight binding model calculations based on the non-equilibrium Green's function approach. The difference in density of state of two ferromagnetic leads and the bias dependence of the propagator cause intrinsic asymmetries in TMR and dynamical conductance at finite bias. Besides, we have displayed that large TMR can be obtained even at high bias for half metallic leads.