Abstract

There is evidence that the α-synucleinopathies Parkinson’s disease (PD) and the Parkinson variant of multiple system atrophy (MSA-P) overlap at multiple levels. Both disorders are characterized by deposition of abnormally phosphorylated fibrillar α-synuclein within the central nervous system suggesting shared pathophysiological mechanisms. Currently, there is no disease-modifying treatment for MSA. In other senses, it has been previously shown that next-generation active vaccination technology with short peptides, AFFITOPEs®, was effective in two transgenic models of synucleinopathies at reducing behavioral deficits, α-syn accumulation and inflammation. Recently, it is shown that there is a crucial contradiction within von Neumann’s theory [K. Nagata and T. Nakamura, Int. J. Theor. Phys. 49, 162 (2010)]. We derive a proposition concerning a quantum expected value under the assumption of the existence of the directions in a spin-1/2 system. The quantum predictions within the formalism of von Neumann’s projective measurement cannot coexist with the proposition concerning the existence of the directions. Therefore, we have to give up either the existence of the directions or the formalism of von Neumann’s projective measurement. Hence, there is a crucial contradiction within von Neumann’s theory. We discuss that this crucial contradiction makes the theoretical formulation of Deutsch’s algorithm questionable. Especially, we systematically describe our assertion based on more mathematical analysis using raw data. We demonstrate here for the first time a drug discovery platform for the generation of analogues of the heptapeptide H-Arg-Lys-Val-MePhe-Tyr-Thr-Trp- OH2, an novel multitargeted inhibitors of Aβ-peptide aggregation, to cross-react with α-synuclein interfering with its fibril formation through novel Aggregation simulated studies on Amyloid β-sheet helix-rich Val-Gly-Gly-Ala-Thr-Thr-Thr-Gly-Val-Thr peptide mimic modulators of α-Synuclein aggregation as a emerging template for drug discovery in α-synucleinopathy interfering amyloidogenesis pathways.

Keywords

Aggregation simulated studies, Amyloid β-sheet helix-richpeptide, mimic modulators, α-Synuclein, aggregation, emerging template, drug discovery, α-synucleinopathies, interfering amyloidogenesis pathways, Can Von Neumann’s Theory, Meet Quantum, Aggregation Computation, simulated studies, on Amyloid β-sheet helix-rich Val-Gly-Gly-Ala-Thr-Thr-Thr-Gly-Val-Thr, peptide mimic, modulators, α-Synuclein aggregation, emerging template.

Abstract

A statistical-mechanical framework for estimation of solvation entropies and enthalpies is proposed, which is based on the analysis of water as a mixture of correlated water oxygens and water hydrogens. Entropic contributions of increasing order are cast in terms of a Mutual Information Expansion that is evaluated to pairwise interactions. In turn, the enthalpy is computed directly from a distance-based hydrogen bonding energy algorithm. The resulting expressions are employed for grid-based analyses of Molecular Dynamics simulations. In this first assessment of the methodology, we obtained global estimates of the excess entropy and enthalpy of water that are in good agreement with experiment and examined the method’s ability to enable detailed elucidation of solvation thermodynamic structures, which can provide valuable knowledge toward molecular design.An algorithm for high-resolution refinement and binding affinity estimation of inhibitors of CGQMCTVWCSSGC targeted conserved peptide substitution mimetic pharmacostructures antagonizing VEGFR-3-mediated oncogenic effects.

Keywords

Estimation, olvation Entropy, Enthalpy, Analysis, Water, Oxygen–Hydrogen Correlations, algorithm, high-resolution refinement, binding affinity, inhibitors, CGQMCTVWCSSGC targeted, conserved peptide, substitution, mimetic, pharmacostructures, antagonizing, VEGFR-3-mediated oncogenic effects,

Abstract

A quantum computer (QC) can operate in parallel on all its possible inputs at once, but the amount of information that can be extracted from the result is limited by the phenomenon of wave function collapse. We present a new computational model, which differs from a QC only in that the result of a measurement is the expectation value of the observable, rather than a random eigenvalue thereof. Such an expectation value QC can solve nondeterministic polynomial-time complete problems in polynomial time. This observation is significant precisely because the computational model can be realized, to a certain extent, by NMR spectroscopy on macroscopic ensembles of quantum spins, namely molecules in a test tube. This is made possible by identifying a manifold of statistical spin states, called pseudo-pure states, the mathematical description of which is isomorphic to that of an isolated spin system. The result is a novel NMR computer that can be programmed much like a QC, but in other respects more closely resembles a DNA computer. Most notably, when applied to intractable combinatorial problems, an NMR computer can use an amount of sample, rather than time, which grows exponentially with the size of the problem. Although NMR computers will be limited by current technology to exhaustive searches over only 15 to 20 bits, searches over as much as 50 bits are in principle possible, and more advanced algorithms could greatly extend the range of applicability of such machines. Cancer is still a major cause of death in the world at the beginning of the- 21st century and remains a major focus for ongoing research and development. In recent years a promising approach to the therapeutic intervention of cancer has focused on antiangiogenesis therapies. VEGFR-3 was detected in advanced human malignancies and correlated with poor prognosis. Previous studies show that activation of the VEGF-C/VEGFR-3 axis promotes cancer metastasis and is associated with clinical progression in patients with lung cancer, indicating that VEGFR-3 is a potential target for cancer therapy. Initial screening has identified other promising VEGFR-3 binding peptides as well. For example, a peptide comprising any of the following amino acid sequences: SGYWWDTWF, SCYWRDTWF, KVGWSSPDW, FVGWTKVLG, YSSSMRWRH, RWRGNAYPG, SAVFRGRWL, WFSASLRFR, and conservative substitution-analogs thereof, binds human VEGFR-3. On the other hand a newly introduced binding energy funnel ‘steepness score’ was applied for the evaluation of the protein–peptide-multi-ligand complexes binding affinity. KNIME-based BiogenetoligandorolTM – Pepcrawler simulations predicted high binding affinity for native protein–peptide-hyper-ligand complexes benchmark and low affinity for low-energy decoy complexes. As a result we managed finally to introduce an algorithm for high-resolution refinement and binding affinity estimation of novel designed inhibitors consisting of CGQMCTVWCSSGC conserved peptide substitution mimetic linked pharmacostructures with potential antagonizing VEGFR-3-mediated oncogenic effects.

Keywords

fast RRT-based algorithm, high-resolution, refinement, binding affinity, estimation, peptide inhibitors, in silico, discovery, performing high resolution, docking refinement, estimation affinity, conserved peptide, substitution, mimetic pharmacostructure, suppressor VEGFR-3 activity, antagonize VEGFR-3-mediated, oncogenic effects, ensemble quantum computing, NMR spectroscopy, high-resolution, refinement, binding affinity, estimation inhibitors, quantum computing, DNA computing, nondeterministic polynomial-time complete,

Abstract

Given a perfect superposition of states on a quantum system of qubits. We propose a fast quantum algorithm for collapsing the perfect superposition to a chosen quantum state without applying any measurements. The basic idea is to use a phase destruction mechanism. Two operators are used, the first operator applies a phase shift and a temporary entanglement to mark in the superposition, and the second operator applies selective phase shifts on the states in the superposition according to their Hamming distance with . The generated state can be used as an excellent input state for testing quantum memories and linear optics quantum computers. We make no assumptions about the used operators and applied quantum gates, but our result implies that for this purpose the number of qubits in the quantum register offers no advantage, in principle, over the obvious measurement-based feedback protocol for the in silico designed of an Anticancer Peptide SVS-1 multipharmacophore as a potential drug-like efficator in Preceding Membrane Neutralization using a web server multi-mimotopic algorithmic approach for biclustering analysis of expression data. Anticancer peptides (ACPs) are polycationic amphiphiles capable of preferentially killing a widespectrum of cancer cells relative to non-cancerous cells. Their primary mode of action is aninteraction with the cell membrane and subsequent activation of lytic effects, however it remainscontroversial the exact mechanism responsible for this mode of action. It has in previous studies been shown that utilizing zeta potential analyses it was possible to demonstrate the interaction of a small anticancer peptide with membrane modelsystems and cancer cells. Electrostatic interactions have a pivotal role in the cell killing processand in contrast to the AMPs action cell death occurs without achieving full neutralization of themembrane charge. The advent of microarray technology has revolutionized the search for genes that are differentially expressed across a range of cell types or experimental conditions. Traditional clustering methods, such as hierarchical clustering, are often difficult to deploy effectively since genes rarely exhibit similar expression pattern across a wide range of conditions. Web-enabled service called GEMS (Gene Expression Mining Server) for biclustering microarray data where Users may upload expression data and specify a set of criteria.GEMS performs bicluster mining based on a Gibbs sampling paradigm. Here, in Biogenea we have for the first time discovered an Anticancer Peptide SVS-1 multipharmacophore with an ini silico evaluated Efficacy in Preceding Membrane Neutralization using a web server for biclustering analysis of expression data.

Keywords

In silico designed, Anticancer Peptide, SVS-1, multipharmacophore, potential drug-like efficator, Preceding Membrane Neutralization, web server, multi-mimotopic, algorithmic, biclustering analysis, expression data, Superposition, Chosen Quantum State, Measurement, In silico, designed,

Abstract

Molecular dynamics (MD) simulation is an emerging in silico technique with potential applications in diverse areas of pharmacology. Over the past three decades MD has evolved as an area of importance for understanding the atomic basis of complex phenomena such as molecular recognition, protein folding, and the transport of ions and small molecules across membranes. The application of MD simulations in isolation and in conjunction with experimental approaches have provided an increased understanding of protein structure-function relationships and demonstrated promise in drug discovery. In this study, Molecular dynamics simulations are applied from structure function relationships to αn advanced fragment-based multi-dimensional chemico-informatic drug discovery approach on a ex vivo derivation and expansion of human neuropoietic cell progenitors using highly conserved poly-peptidomimic linked-pharmacophores targeted to neural pathways for neurodegenerative disease modeling.

Keywords

Molecular dynamics, simulations, structure, function relationships, drug discovery, Ex vivo, derivation, expansion, human neuropoietic cell progenitors, highly conserved poly-peptidomimic, linked-pharmacophores, neural pathways, neurodegenerative, disease modeling, advanced fragment-based, multi-dimensional, chemico-informatic, approach, molecular dynamics simulations, Cytochrome P450, Drug-drug interactions, Genetic polymorphism, Drug design, Allosteric binding sites, Cryptic binding sites.

Abstract

The existence of any elementary particle in universe requires the existence of some region of universe occupied by it. By taking the volume of this occupied region, the author will reformulate the relativistic quantum field theory using new 3-dimensional region-like idealization of elementary particles and hereinafter will call the total volume of all regions occupied by the elementary constituent particles of the quantum system the occupied volume. Also the author will call the set of all regions of universe filled by elementary constituent particles of the quantum system the occupied path. Always any quantum system is existed at a head of its occupied path. This path is growing by mutual filling and leaving regions of universe by its elementary constituent particles. The conservation of this elementary constituent particle requires the conservation of its occupied volume during this process. This requirement could be summarized by the following conditions: 1) the total volume of all regions of universe filled by the elementary constituent particles of the quantum system minus the total volume of all regions of universe left by these elementary constituent particles must be equal to the occupied volume of the quantum system; 2) the total increase in the occupied volume of the quantum system due to the absorption of another elementary particles from outside its occupied regions minus the total decreasing in its occupied volume due to the emission of another elementary particles outside its occupied regions must be equal to the occupied volume of human neuropoietic cell progenitors using highly conserved poly-peptidomimic linked-pharmacophores targeted to neural pathways for neurodegenerative disease modeling. An advanced fragment-based multi-dimensional chemico-informatic approach The wave-particle duality of the elementary constituent particles implied accumulation of them as the finite set of interfered waves. This accumulation of elementary constituent particles causes the absolute probabilistic nature of event of finding the elementary consistent particle in specified interfered wave, and hence the mathematical representation of this interfered wave should take into account the value of probability amplitude of finding an elementary particle inside the region occupied specified interfered wave. In quantum theory this probability amplitude corresponds to complex amplitude of the wave function of interfered wave. Also in Hilbert’s representation of the quantum theory these wave functions are representing the components of the quantum state vector. In this paper the author will develop the transformation theory of the region-like quantum state of the quantum system for the Reformulation of Relativistic Quantum Field Theory using an advanced fragment-based multi-dimensional chemico-informatic Region-Like Idealization approach of the ex vivo derivation and expansion of Eeentary Particle human neuropoietic cell progenitors on highly conserved poly-peptidomimic linked-pharmacophores targeted to neural pathways for neurodegenerative disease modeling.

Keywords

Reformulation of Relativistic Quantum Field Theory Using Region-Like Idealization of the Elementary ParticleEx vivo derivation and expansion of human neuropoietic cell progenitors using highly conserved poly-peptidomimic linked-pharmacophores targeted to neural pathways for neurodegenerative disease modeling. An advanced fragment-based multi-dimensional chemico-informatic approach, Region-Like Idealization, Creation, Annihilation, Animation, Occupied Volume, Occupied Path, Relativistic Quantum Field Theory,

Abstract

Molecular dynamics (MD) simulation is an emerging in silico technique with potential applications in diverse areas of pharmacology. Over the past three decades MD has evolved as an area of importance for understanding the atomic basis of complex phenomena such as molecular recognition, protein folding, and the transport of ions and small molecules across membranes. In this study the application of MD simulations in isolation and in conjunction with experimental approaches have provided an increased understanding of protein structure-function relationships and demonstrated promise in drug discovery of a novel multi-chemo-structure super-agonistic CellshOX Decoy Peptide Mimetic Construct as a Human Umbilical Cord blood Stem Cell Expansion Molecule in a QSAR automating modeling lead compound design approach.

Keywords

Molecular dynamics simulations, structure, function relationships, drug discovery, in silico discovery, novel multi-chemo-structure, super-agonistic, CellshOX, Decoy Peptide, Mimetic Construct, Human Umbilical, Cord blood, Stem Cell Expansion, Molecule, QSAR automating modeling, lead compound, design approach.

Abstract

In this paper, I shall sketch a new way to consider a Lindenbaum-Tarski algebra as a 3D logical space in which any one (of the 256 statements) occupies a well-defined position and it is identified by a numerical ID. This allows pure mechanical computation both for generating rules and inferences. It is shown that this abstract formalism can be geometrically represented with logical spaces and subspaces allowing a vectorial representation. Finally, it shows the application to quantum computing through the example of three coupled harmonic oscillators of a novel multi-chemo-structure super-agonistic CellshOX Decoy Peptide Mimetic Construct as a Human Umbilical Cord blood Stem Cell Expansion Molecule in a QSAR automating modeling lead compound design approach.

Keywords

Lindenbaum-Tarski Algebra; 3D Logical Space; Mechanical Computation; Inference; Quantum Computing; Raising Operators; Lowering Operators; Implement Quantum Computation; In silico discovery; multi-chemo-structure; super-agonistic; CellshOX; Decoy Peptide; Mimetic Construct; Human Umbilical Cord blood; Stem Cell Expansion Molecule; QSAR automating modeling; lead compound; design approach;

Abstract

A kind of novel three-party quantum secure direct communication protocol is proposed with the correlation of two-particle entangled state. In this scheme the qubit transmission forms a closed loop and every one of the three participants is both a receiver and a sender of particle sequences in the bidirectional quantum channels. Each party implements the corresponding unitary operations according to its secret bit value over the quantum channels and then extracts the other two parties’ unitary operations by performing Bell measurements on the encoded particles. Thus they can obtain the secret information simultaneously. Finally, our security analysis in this paper shows that the present three-party scheme is a secure in silico discovery protocol of a novel multi-chemo-structure super-agonistic CellshOX Decoy Peptide Mimetic Construct as a Human Umbilical Cord blood Stem Cell Expansion Molecule in a QSAR automating modeling lead compound design approach.

Keywords

Three-Party Simultaneous; Quantum Secure Communication Based; Closed TransmissionI; n silico discovery; novel multi-chemo-structure; super-agonistic; CellshOX Decoy; Peptide Mimetic; Construct; Human Umbilical Cord blood; Stem Cell Expansion Molecule; QSAR automating modeling; lead compound design approach;

Abstract

Molecular simulation is increasingly demonstrating its practical value in the investigation of biological systems. Computational modelling of biomolecular systems is an exciting and rapidly developing area, which is expanding significantly in scope. A range of simulation methods has been developed that can be applied to study a wide variety of problems in structural biology and at the interfaces between physics, chemistry and biology. Here, we give an overview of methods and some recent developments in atomistic biomolecular simulation. Some recent applications and theoretical developments are highlighted.Biomolecular simulation and modelling: status, progress and prospects on a Computational mining Biomolecular simulation modelling combined molecular docking-based and pharmacophore-based target prediction strategy through a probabilistic fusion method for target ranking of anti-HIV-I P24-derived peptide mimic promising pharmacophores.

Keywords

Biomolecular simulation΄; modelling status; progress; prospects; computational mining approach; combined molecular docking-based; pharmacophore-based; target prediction strategy; probabilistic fusion method; target ranking; anti-HIV-I; P24-derived; peptide mimic; pharmacophores; biomolecular simulation; molecular modelling; molecular dynamics; force fields; quantum mechanics/molecular mechanics; quantum chemical modelling