Molecular modelling studies of binding of DACD derivatives into G-Quadruplex DNA: comparison of force field and quantum polarized ligand docking methods

The DNA G-qadruplexes are one of the targets being actively explored for anti-cancer therapy by inhibiting them through small molecules. This computational study was conducted to predict the binding strengths and orientations of a set of novel dimethyl-amino-ethyl-acridine (DACA) analogues that are designed and synthesized in our laboratory, but did not diffract in Synchrotron light.Thecrystal structure of DNA G-Quadruplex(TGGGGT)4(PDB: 1O0K) was used as target for their binding properties in our studies.We used both the force field (FF) and QM/MM derived atomic charge schemes simultaneously for comparing the predictions of drug binding modes and their energetics. This study evaluates the comparative performance of fixed point charge based Glide XP docking and the quantum polarized ligand docking schemes. These results will provide insights on the effects of including or ignoring the drug-receptor interfacial polarization events in molecular docking simulations, which in turn, will aid the rational selection of computational methods at different levels of theory in future drug design programs. Plenty of molecular modelling tools and methods currently exist for modelling drug-receptor or protein-protein, or DNA-protein interactionssat different levels of complexities.Yet, the capasity of such tools to describevarious physico-chemical propertiesmore accuratelyis the next step ahead in currentresearch.Especially, the usage of most accurate methods in quantum mechanics(QM) is severely restricted by theirtedious nature. Though the usage of massively parallel super computing environments resulted in a tremendous improvement in molecular mechanics (MM) calculations like molecular dynamics,they are still capable of dealing with only a couple of tens to hundreds of atoms for QM methods. One such efficient strategy that utilizes thepowers of both MM and QM are the QM/MM hybrid methods. Lately, attempts have been directed towards the goal of deploying several different QM methods for betterment of force field based simulations, but with practical restrictions in place. One of such methods utilizes the inclusion of charge polarization events at the drug-receptor interface, that is not explicitly present in the MM FF.

Electronic properties of liquid hydrogen fluoride: A sequential quantum mechanical/Born-Oppenheimer molecular dynamics approach

The electronic properties of liquid hydrogen fluoride (HF) were investigated by carrying out sequential quantum mechanics/Born-Oppenheimer molecular dynamics. The structure of the liquid is in good agreement with recent experimental information. Emphasis was placed on the analysis of polarisation effects, dynamic polarisability and electronic excitations in liquid HF. Our results indicate an increase in liquid phase of the dipole moment (similar to 0.5 D) and isotropic polarisability (5%) relative to their gas-phase values. Our best estimate for the first vertical excitation energy in liquid HF indicates a blue-shift of 0.4 +/- 0.2 eV relative to that of the gas-phase monomer (10.4 eV). (C) 2010 Elsevier B.V. All rights reserved.

Canonical quantum potential scattering theory

A new formulation of potential scattering in quantum mechanics is developed using a close structural analogy between partial waves and the classical dynamics of many non-interacting fields. Using a canonical formalism we find nonlinear first-order differential equations for the low-energy scattering parameters such as scattering length and effective range. They significantly simplify typical calculations, as we illustrate for atom-atom and neutron-nucleus scattering systems. A generalization to charged particle scattering is also possible.

Genesis of quantum nonlocality

We revisit the problem of an otherwise classical particle immersed in the zero-point radiation field, with the purpose of tracing the origin of the nonlocality characteristic of Schrodinger`s equation. The Fokker-Planck-type equation in the particles phase-space leads to an infinite hierarchy of equations in configuration space. In the radiationless limit the first two equations decouple from the rest. The first is the continuity equation: the second one, for the particle flux, contains a nonlocal term due to the momentum fluctuations impressed by the field. These equations are shown to lead to Schrodinger`s equation. Nonlocality (obtained here for the one-particle system) appears thus as a property of the description, not of Nature. (C) 2011 Elsevier B.V. All rights reserved.

Aspects of classical and quantum motion on a flux cone

Motion of a nonrelativistic particle on a cone with a magnetic flux running through the cone axis (a flux cone) is studied. It is expressed as the motion of a particle moving on the Euclidean plane under the action of a velocity-dependent force. The probability fluid (quantum flow) associated with a particular stationary state is studied close to the singularity, demonstrating nontrivial Aharonov-Bohm effects. For example, it is shown that, near the singularity, quantum flow departs from classical flow. In the context of the hydrodynamical approach to quantum mechanics, quantum potential due to the conical singularity is determined, and the way it affects quantum flow is analyzed. It is shown that the winding number of classical orbits plays a role in the description of the quantum Bow. The connectivity of the configuration space is also discussed.

Time evolution of the Wigner function in discrete quantum phase space for a soluble quasi-spin model

The discrete phase space approach to quantum mechanics of degrees of freedom without classical counterparts is applied to the many-fermions/quasi-spin Lipkin model. The Wi:ner function is written for some chosen states associated to discrete angle and angular momentum variables, and the rime evolution is numerically calculated using the discrete von Neumnnn-Liouville equation. Direct evidences in the lime evolution of the Wigner function are extracted that identify a tunnelling effect. A connection with a SU(2)-based semiclassical continuous approach to the Lipkin model is also presented.

Quantum topology change and large-N gauge theories

We study a model for dynamical localization of topology using ideas from non-commutative geometry and topology in quantum mechanics. We consider a collection X of N one-dimensional manifolds and the corresponding set of boundary conditions (self-adjoint extensions) of the Dirac operator D. The set of boundary conditions encodes the topology and is parameterized by unitary matrices g. A particular geometry is described by a spectral triple x(g) = (A X, script H sign X, D(g)). We define a partition function for the sum over all g. In this model topology fluctuates but the dimension is kept fixed. We use the spectral principle to obtain an action for the set of boundary conditions. Together with invariance principles the procedure fixes the partition function for fluctuating topologies. The model has one free-parameter β and it is equivalent to a one plaquette gauge theory. We argue that topology becomes localized at β = ∞ for any value of N. Moreover, the system undergoes a third-order phase transition at β = 1 for large-N. We give a topological interpretation of the phase transition by looking how it affects the topology. © SISSA/ISAS 2004.

Gravity and the quantum: Are they reconcilable?

General relativity and quantum mechanics are not consistent with each other. This conflict stems from the very fundamental principles on which these theories are grounded. General relativity, on one hand, is based on the equivalence principle, whose strong version establishes the local equivalence between gravitation and inertia. Quantum mechanics, on the other hand, is fundamentally based on the uncertainty principle, which is essentially nonlocal. This difference precludes the existence of a quantum version of the strong equivalence principle, and consequently of a quantum version of general relativity. Furthermore, there are compelling experimental evidences that a quantum object in the presence of a gravitational field violates the weak equivalence principle. Now it so happens that, in addition to general relativity, gravitation has an alternative, though equivalent, description, given by teleparallel gravity, a gauge theory for the translation group. In this theory torsion, instead of curvature, is assumed to represent the gravitational field. These two descriptions lead to the same classical results, but are conceptually different. In general relativity, curvature geometrizes the interaction while torsion, in teleparallel gravity, acts as a force, similar to the Lorentz force of electrodynamics. Because of this peculiar property, teleparallel gravity describes the gravitational interaction without requiring any of the equivalence principle versions. The replacement of general relativity by teleparallel gravity may, in consequence, lead to a conceptual reconciliation of gravitation with quantum mechanics. © 2006 American Institute of Physics.

De Sitter relativity and quantum physics

In the presence of a cosmological constant, interpreted as a purely geometric entity, absence of matter is represented by a de Sitter spacetime. As a consequence, ordinary Poincaré special relativity is no longer valid and must be replaced by a de Sitter special relativity. By considering the kinematics of a spinless particle in a de Sitter spacetime, we study the geodesics of this spacetime, the ensuing definitions of canonical momenta, and explore possible implications for quantum mechanics. © 2007 American Institute of Physics.

Non-Markovian expansion in quantum Brownian motion

We consider the non-Markovian Langevin evolution of a dissipative dynamical system in quantum mechanics in the path integral formalism. After discussing the role of the frequency cutoff for the interaction of the system with the heat bath and the kernel and noise correlator that follow from the most common choices, we derive an analytic expansion for the exact non-Markovian dissipation kernel and the corresponding colored noise in the general case that is consistent with the fluctuation-dissipation theorem and incorporates systematically non-local corrections. We illustrate the modifications to results obtained using the traditional (Markovian) Langevin approach in the case of the exponential kernel and analyze the case of the non-Markovian Brownian motion. We present detailed results for the free and the quadratic cases, which can be compared to exact solutions to test the convergence of the method, and discuss potentials of a general nonlinear form. © 2013 Elsevier B.V. All rights reserved.

Entropy effect in quantum computing and information: an open-source environment simulation

The technologies are rapidly developing, but some of them present in the computers, as for instance their processing capacity, are reaching their physical limits. It is up to quantum computation offer solutions to these limitations and issues that may arise. In the field of information security, encryption is of paramount importance, being then the development of quantum methods instead of the classics, given the computational power offered by quantum computing. In the quantum world, the physical states are interrelated, thus occurring phenomenon called entanglement. This study presents both a theoretical essay on the merits of quantum mechanics, computing, information, cryptography and quantum entropy, and some simulations, implementing in C language the effects of entropy of entanglement of photons in a data transmission, using Von Neumann entropy and Tsallis entropy.

Quantum confinement in hydrogen bond

In this work, the quantum confinement effect is proposed as the cause of the displacement of the vibrational spectrum of molecular groups that involve hydrogen bonds. In this approach, the hydrogen bond imposes a space barrier to hydrogen and constrains its oscillatory motion. We studied the vibrational transitions through the Morse potential, for the NH and OH molecular groups inside macromolecules in situation of confinement (when hydrogen bonding is formed) and nonconfinement (when there is no hydrogen bonding). The energies were obtained through the variational method with the trial wave functions obtained from supersymmetric quantum mechanics formalism. The results indicate that it is possible to distinguish the emission peaks related to the existence of the hydrogen bonds. These analytical results were satisfactorily compared with experimental results obtained from infrared spectroscopy. (c) 2015 Wiley Periodicals, Inc.

Quantum confinement in hydrogen bond of DNA and RNA

The hydrogen bond is a fundamental ingredient to stabilize the DNA and RNA macromolecules. The main contribution of this work is to describe quantitatively this interaction as a consequence of the quantum confinement of the hydrogen. The results for the free and confined system are compared with experimental data. The formalism to compute the energy gap of the vibration motion used to identify the spectrum lines is the Variational Method allied to Supersymmetric Quantum Mechanics.

Ab initio quantum mechanical investigation of structural and chemical-physical properties of selected minerals for minero-petrological, structural ceramic and biomaterial applications

The purpose of this thesis is the atomic-scale simulation of the crystal-chemical and physical (phonon, energetic) properties of some strategically important minerals for structural ceramics, biomedical and petrological applications. These properties affect the thermodynamic stability and rule the mineral-environment interface phenomena, with important economical, (bio)technological, petrological and environmental implications. The minerals of interest belong to the family of phyllosilicates (talc, pyrophyllite and muscovite) and apatite (OHAp), chosen for their importance in industrial and biomedical applications (structural ceramics) and petrophysics. In this thesis work we have applicated quantum mechanics methods, formulas and knowledge to the resolution of mineralogical problems ("Quantum Mineralogy”). The chosen theoretical approach is the Density Functional Theory (DFT), along with periodic boundary conditions to limit the portion of the mineral in analysis to the crystallographic cell and the hybrid functional B3LYP. The crystalline orbitals were simulated by linear combination of Gaussian functions (GTO). The dispersive forces, which are important for the structural determination of phyllosilicates and not properly con-sidered in pure DFT method, have been included by means of a semi-empirical correction. The phonon and the mechanical properties were also calculated. The equation of state, both in athermal conditions and in a wide temperature range, has been obtained by means of variations in the volume of the cell and quasi-harmonic approximation. Some thermo-chemical properties of the minerals (isochoric and isobaric thermal capacity) were calculated, because of their considerable applicative importance. For the first time three-dimensional charts related to these properties at different pressures and temperatures were provided. The hydroxylapatite has been studied from the standpoint of structural and phonon properties for its biotechnological role. In fact, biological apatite represents the inorganic phase of vertebrate hard tissues. Numerous carbonated (hydroxyl)apatite structures were modelled by QM to cover the broadest spectrum of possible biological structural variations to fulfil bioceramics applications.

Optical quantum random number generator

A physical random number generator based on the intrinsic randomness of quantum mechanics is described. The random events are realized by the choice of single photons between the two outputs of a beamsplitter. We present a simple device, which minimizes the impact of the photon counters’ noise, dead-time and after pulses.