Quantum binding energies of checkpoint CTLA-4 in complex with the immuno-oncological drug ipilimumab.

Inhibition of the checkpoint protein CTLA-4 by the US-FDA's approved monoclonal antibody ipilimumab has delivered breakthrough therapies against a wide range of cancers, being an important issue for clinical research. To date, many structural properties of this drug have been unveiled. However, the binding energy features of the receptor CTLA-4 in complex with its drug inhibitor, based on crystallographic data, need a deeper understanding. Within this context, by employing quantum chemistry we investigate in silico the binding energy features of the checkpoint protein CTLA-4 in complex with its drug inhibitor, highlighting the most relevant residue-residue interactions, looking for new insights into the mechanisms of pathway blockade to further engineer its affinity and selectivity. Our computational results not only give a better understanding of the binding mechanisms, but also point to an efficient alternative towards the development of antibody-based drugs, leading to new treatments for cancer therapy based upon immunotherapy.

Blockade of the checkpoint PD-1 by its ligand PD-L1 and the immuno-oncological drugs pembrolizumab and nivolumab.

We investigate the interaction between the programmed cell death protein 1 (PD-1) and the programmed cell death ligand 1 (PD-L1), as well as the immuno-oncological drugs pembrolizumab (PEM), and nivolumab (NIV), through quantum chemistry methods based on the Density Functional Theory (DFT) and the molecular fractionation with conjugate caps (MFCC) scheme, in order to map their hot-spot regions. Our results showed that the total interaction energy order of the three complexes is in good agreement with the experimental binding affinity order: PD-1/PEM > PD-1/NIV > PD-1/PD-L1. Besides, a detailed investigation revealed the energetically most relevant residue-residue pairs-interaction for each complex. Our computational results give a better understanding of the interaction mechanism between the protein PD-1 and its ligands (natural and inhibitors), unleashing the immune surveillance to destroy the cancer cells by decreasing their immune evasion. They are also an efficient alternative towards the development of new small-molecules and antibody-based drugs, pointing out to new treatments for cancer therapy.

Critical properties of the SIS model on the clustered homophilic network.

The spreading of epidemics in complex networks has been a subject of renewed interest of several scientific branches. In this regard, we have focused our attention on the study of the susceptible-infected-susceptible (SIS) model, within a Monte Carlo numerical simulation approach, representing the spreading of epidemics in a clustered homophilic network. The competition between infection and recovery that drives the system either to an absorbing or to an active phase is analyzed. We estimate the static critical exponents ß ∕ ν , 1 ∕ ν and γ ∕ ν , through finite-size scaling (FSS) analysis of the order parameter ρ and its fluctuations, showing that they differ from those associated with the contact process on a scale-free network, as well as those predicted by the heterogeneous mean-field theory.

Vibrational Spectroscopy and Phonon-Related Properties of the L-Aspartic Acid Anhydrous Monoclinic Crystal.

The infrared absorption and Raman scattering spectra of the monoclinic P21 l-aspartic acid anhydrous crystal were recorded and interpreted with the help of density functional theory (DFT) calculations. The effect of dispersive forces was taken into account, and the optimized unit cells allowed us to obtain the vibrational normal modes. The computed data exhibits good agreement with the measurements for low wavenumbers, allowing for a very good assignment of the infrared and Raman spectral features. The vibrational spectra of the two lowest energy conformers of the l-aspartic molecule were also evaluated using the hybrid B3LYP functional for the sake of comparison, showing that the molecular calculations give a limited description of the measured IR and Raman spectra of the l-aspartic acid crystal for wavenumbers below 1000 cm(-1). The results obtained reinforce the need to use solid-state calculations to describe the vibrational properties of molecular crystals instead of calculations for a single isolated molecule picture even for wavenumbers beyond the range usually associated with lattice modes (200 cm(-1) < ω < 1000 cm(-1)).

Anhydrous crystals of DNA bases are wide gap semiconductors.

We present the structural, electronic, and optical properties of anhydrous crystals of DNA nucleobases (guanine, adenine, cytosine, and thymine) found after DFT (Density Functional Theory) calculations within the local density approximation, as well as experimental measurements of optical absorption for powders of these crystals. Guanine and cytosine (adenine and thymine) anhydrous crystals are predicted from the DFT simulations to be direct (indirect) band gap semiconductors, with values 2.68 eV and 3.30 eV (2.83 eV and 3.22 eV), respectively, while the experimentally estimated band gaps we have measured are 3.83 eV and 3.84 eV (3.89 eV and 4.07 eV), in the same order. The electronic effective masses we have obtained at band extremes show that, at low temperatures, these crystals behave like wide gap semiconductors for electrons moving along the nucleobases stacking direction, while the hole transport are somewhat limited. Lastly, the calculated electronic dielectric functions of DNA nucleobases crystals in the parallel and perpendicular directions to the stacking planes exhibit a high degree of anisotropy (except cytosine), in agreement with published experimental results.

C60-derived nanobaskets: stability, vibrational signatures, and molecular trapping.

C(60)-derived nanobaskets, with chemical formulae (symmetry point group) C(40)H(10) (C(5v)), C(39)H(12) (C(3v)), C(46)H(12) (C(2v)), were investigated. Molecular dynamic simulations (MDSs) indicate that the molecules preserve their bonding frame for temperatures up to 300 K (simulation time 100 ps), and maintain atomic cohesion for at least 4 ps at temperatures up to 3500 K. The infrared spectra of the C(60)-derived nanobaskets were simulated through density functional theory (DFT) calculations, allowing for the attribution of infrared signatures specific to each carbon nanobasket. The possibility of using C(60)-derived nanobaskets as molecular containers is demonstrated by performing a DFT study of their bonding to hydrogen, water, and L-alanine. The carbon nanostructures presented here show a higher bonding energy (approximately 1.0 eV), suggesting that a family of nanostructures, C(n)-derived (n = 60,70,76,80, etc) nanobaskets, could work as molecular containers, paving the way for future developments such as tunable traps for complex molecular systems.

Free-electron gas in the Apollonian network: multifractal energy spectrum and its thermodynamic fingerprints.

We study the free-electron gas in an Apollonian network within the tight-binding framework. The scale-free and small-world character of the underlying lattice is known to result in a quite structured energy spectrum with deltalike singularities, gaps, and minibands. After an exact numerical diagonalization of the corresponding adjacency matrix of the network with a finite number of generations, we employ a scaling analysis of the moments of the density of states to characterize its multifractality and report the associated singularity spectrum. The fractal nature of the energy spectrum is also shown to be reflected in the thermodynamic behavior by logarithmic modulations on the temperature dependence of the specific heat. The absence of chiral symmetry of the Apollonian network leads to distinct thermodynamic behaviors due to electrons and holes thermal excitations.

Adsorption of ascorbic acid on the C60 fullerene.

Adsorption of ascorbic acid (AsA) on C60 is investigated using classical molecular mechanics and density functional theory (DFT). Classical annealing was performed to explore the space of molecular configurations of ascorbic acid adsorbed on C60, searching for optimal geometries. From the structure with the smallest total energy, 10 initial configurations were prepared by applying rotations of 90 degrees about three orthogonal axes. Each one of these configurations was optimized using DFT (for both LDA and GGA exchange-correlation functionals), and an estimate of their total and adsorption energies was found. Different configurations have minimal adsorption energies (defined here as the total energy of the adsorbate minus the total energy of the separate molecules) from -0.54 to -0.10 eV, with distinct optimal distances between the AsA and C60 centers of mass. According to a Hirshfeld population analysis, AsA is, in general, an acceptor of electrons from C60. Our results demonstrate the feasibility of noncovalent functionalization of C60 with AsA and provide minimal energy values for the several different configurations investigated. These results should be considered in reactions as a possible way to prevent against the oxidative damage and toxicity of C60. The beneficial effects of using AsA-C60 includes its action when administered together with levodopa, against the neurotoxicity generated by levodopa isolated, which opens new strategies for the Parkinson's disease treatment.

Molecular modelling and quantum biochemistry computations of a naturally occurring bioremediation enzyme: Alkane hydroxylase from Pseudomonas putida P1.

Many species of bacteria involved in degradation of n-alkanes have an important constitutional metabolic enzyme, the alkane hydroxylase called AlkB, specialized in the conversion of hydrocarbons molecules that can be used as carbon and/or energy source. This enzyme plays an important role in the microbial degradation of oil, chlorinated hydrocarbons, fuel additives, and many other compounds. A number of these enzymes has been biochemically characterized in detail because the potential of alkane hydroxylases to catalyse high added-value reactions is widely recognized. Nevertheless, the industrial and process bioremediation application of them is restricted, owing to their complex biochemistry, challenging process requirements, and the limited number of their three-dimensional structures. Furthermore, AlkB has great potential as biocatalysts for selective transformation of a wide range of chemically inert unreactive alkanes into reactive chemical precursors that can be used as tools for bioremediation and bioprocesses. Aiming to understand the possible ways the AlkB enzyme Pseudomonas putida P1 interacts with octane, octanol and 1-octyne, we consider its suitable biochemical structure taking into account a 3-D homology modelling. Besides, by using a quantum chemistry computational model based on the density functional theory (DFT), we determine possible protein-substrate interaction regions measured by means of its binding energy simulated throughout the Molecular Fractionation with Conjugated Caps (MFCC) approach.

Conformational, Optoelectronic and Vibrational Properties of the Entacapone Molecule: A Quantum Chemistry Study.

A quantum chemistry study were carried out looking for the conformational, optoelectronic and vibrational properties of the entacapone molecule, an efficient drug used in the Parkinson's disease treatment. Classical annealing was performed to explore the entacapone's molecular configurations, searching for optimal geometries. The quantum optimization calculations were made using three different functional combination levels of the density functional theory (DFT). The structural data (bond length, bond and torsion angles), charge population analysis (absorption spectra) and molecular orbital study (HOMO and LUMO) were obtained considering the lower energy optimized conformation of the entacapone molecule. Furthermore, a complete assignment of the harmonic vibrational frequencies were achieved through their infrared (IR) and Raman spectra.

Nucleotide correlations and electronic transport of DNA sequences.

We use a tight-binding formulation to investigate the transmissivity and wave-packet dynamics of sequences of single-strand DNA molecules made up from the nucleotides guanine G , adenine A , cytosine C , and thymine T . In order to reveal the relevance of the underlying correlations in the nucleotides distribution, we compare the results for the genomic DNA sequence with those of two artificial sequences: (i) the Rudin-Shapiro one, which has long-range correlations; (ii) a random sequence, which is a kind of prototype of a short-range correlated system, presented here with the same first-neighbor pair correlations of the human DNA sequence. We found that the long-range character of the correlations is important to the persistence of resonances of finite segments. On the other hand, the wave-packet dynamics seems to be mostly influenced by the short-range correlations.

Sub-diffusive electronic transport in a DNA single-strand chain with electron-phonon coupling.

We investigate the electronic wavepacket dynamics in a finite segment of a DNA single-strand chain considering the electron-phonon coupling. Our theoretical approach makes use of an effective tight-binding Hamiltonian to describe the electron dynamics, together with a classical harmonic Hamiltonian to treat the intrinsic DNA vibrations. An effective time-dependent Schrödinger equation is then settled up and solved numerically for an initially localized wave-packet using the standard Dormand-Prince eighth-order Runge-Kutta method. Our numerical results indicate the presence of a sub-diffusive electronic wavepacket spread mediated by the electron-phonon interaction.

Classical acoustic waves in damped media.

A Green function technique is employed to investigate the propagation of classical damped acoustic waves in complex media. The calculations are based on the linear response function approach, which is very convenient to deal with this kind of problem. Both the displacement and the gradient displacement Green functions are determined. All deformations in the media are supposed to be negligible, so the motions considered here are purely acoustic waves. The damping term gamma is included in a phenomenological way into the wave vector expression. By using the fluctuation-dissipation theorem, the power spectrum of the acoustic waves is also derived and has interesting properties, the most important of them being a possible relation with the analysis of seismic reflection data.

Ising models on the regularized Apollonian network.

We investigate the critical properties of Ising models on a regularized Apollonian network (RAN), here defined as a kind of Apollonian network in which the connectivity asymmetry associated with its corners is removed. Different choices for the coupling constants between nearest neighbors are considered and two different order parameters are used to detect the critical behavior. While ordinary ferromagnetic and antiferromagnetic models on a RAN do not undergo a phase transition, some antiferrimagnetic models show an interesting infinite-order transition. All results are obtained by an exact analytical approach based on iterative partial tracing of the Boltzmann factor as an intermediate step for the calculation of the partition function and the order parameters.

Critical properties of a superdiffusive epidemic process.

We introduce a superdiffusive one-dimensional epidemic process model on which infection spreads through a contact process. Healthy (A) and infected (B) individuals can jump with distinct probabilities D(A) and D(B) over a distance ℓ distributed according to a power-law probability P(ℓ)[proportionality]1/ℓ(µ). For µ≥3 the propagation is equivalent to diffusion, while µ<3 corresponds to Lévy flights. In the D(A)>D(B) diffusion regime, field-theoretical results have suggested a first-order transition, a prediction not supported by several numerical studies. An extensive numerical study of the critical behavior in both the diffusive (µ≥3) and superdiffusive (µ<3) D(A)>D(B) regimes is also reported. We employed a finite-size scaling analysis to obtain the critical point as well as the static and dynamic critical exponents for several values of µ. All data support a second-order phase transition with continuously varying critical exponents which do not belong to the directed percolation universality class.

Structural, electronic and optical properties of ilmenite and perovskite CdSnO3 from DFT calculations.

CdSnO(3) ilmenite and perovskite crystals were investigated using both the local density and generalized gradient approximations, LDA and GGA, respectively, of the density functional theory (DFT). The electronic band structures, densities of states, dielectric functions, optical absorption and reflectivity spectra related to electronic transitions were obtained, as well as the infrared absorption spectra after computing the vibrational modes of the crystals at q = 0. Dielectric optical permittivities and polarizabilities at ω = 0 and ∞ were also calculated. The results show that GGA-optimized geometries are more accurate than LDA ones, and the Kohn-Sham band structures obtained for the CdSnO(3) polymorphs confirm that ilmenite has an indirect band gap, while perovskite has a direct band gap, both being semiconductors. Effective masses for both crystals are obtained for the first time, being highly isotropic for electrons and anisotropic for holes. The optical properties reveal a very small degree of anisotropy of both crystals with respect to different polarization planes of incident light. The phonon calculation at q = 0 for perovskite CdSnO(3) does not show any imaginary frequencies, in contrast to a previous report suggesting the existence of a more stable crystal of perovskite CdSnO(3) with ferroelectric properties.

Fractal spectrum of charge carriers in quasiperiodic graphene structures.

In this work we investigate the interaction of charge carriers in graphene with a series of p-n-p junctions arranged according to a deterministic quasiperiodic substitutional Fibonacci sequence. The junctions create a potential landscape with quantum wells and barriers of different widths, allowing the existence of quasi-confined states. Spectra of quasi-confined states are calculated for several generations of the Fibonacci sequence as a function of the wavevector component parallel to the barrier interfaces. The results show that, as the Fibonacci generation is increased, the dispersion branches form energy bands distributed as a Cantor-like set. Besides, for a quasiperiodic set of potential barriers, we obtain the electronic tunneling probability as a function of energy, which shows a striking self-similar behavior for different generation numbers.

Bose-Einstein condensation in the Apollonian complex network.

We demonstrate that a topology-induced Bose-Einstein condensation (BEC) takes place in a complex network. As a model topology, we consider the deterministic Apollonian network which exhibits scale-free, small-world, and hierarchical properties. Within a tight-binding approach for noninteracting bosons, we report that the BEC transition temperature and the gap between the ground and first excited states follow the same finite-size scaling law. An anomalous density dependence of the transition temperature is reported and linked to the structure of gaps and degeneracies of the energy spectrum. The specific heat is shown to be discontinuous at the transition, with low-temperature modulations as a consequence of the fragmented density of states.

Defects in graphene-based twisted nanoribbons: structural, electronic, and optical properties.

We present some computational simulations of graphene-based nanoribbons with a number of half-twists varying from 0 to 4 and two types of defects obtained by removing a single carbon atom from two different sites. Optimized geometries are found by using a mix of classical quantum semiempirical computations. According with the simulations results, the local curvature of the nanoribbons increases at the defect sites, especially for a higher number of half-twists. The HOMO-LUMO energy gap of the nanostructures has significant variation when the number of half-twists increases for the defective nanoribbons. At the quantum semiempirical level, the first optically active transitions and oscillator strengths are calculated using the full configuration interaction (CI) framework, and the optical absorption in the UV/vis range (electronic transitions) and in the infrared (vibrational transitions) are achieved. Distinct nanoribbons show unique spectral signatures in the UV/vis range, with the first absorption peaks in wavelengths ranging from the orange to the violet. Strong absorption is observed in the ultraviolet region, although differences in their infrared spectra are hardly discernible.