Abstract

Next-generation molecular force fields deliver accurate descriptions of non-covalent interactions by employing more elaborate functional forms than their predecessors. Much work has been dedicated to improving the description of the electrostatic potential (ESP) generated by these force fields. A common approach to improving the ESP is by augmenting the point charges on each center with higher-order multipole moments. The resulting anisotropy greatly improves the directionality of the non-covalent bonding, with a concomitant increase in computational cost. In this work, we develop an efficient strategy for enumerating multipole interactions, by casting an efficient spherical harmonic based approach within a particle mesh Ewald (PME) framework. Although the derivation involves lengthy algebra, the final expressions are relatively compact, yielding an approach that can efficiently handle both finite and periodic systems without imposing any approximations beyond PME. Forces and torques are readily obtained, making our method well suited to modern molecular dynamics simulations. 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. We demonstrate here for the first time an efficient emerging template for drug discovery algorithm for multipole energies and derivatives based on spherical harmonics and extensions to particle α-Synuclein aggregation simulated mesh Ewalds on Amyloid β-sheet helix-rich Val-Gly-Gly-Ala-Thr-Thr-Thr-Gly-Val-Thr peptide mimic modulators in α-synucleinopathy interfering amyloidogenesis pathways.

Keywords

Aggregation simulated studies;Amyloid β-sheet; helix-richpeptide; mimic modulators;α-Synuclein; aggregation;emerging templated;rug discovery;α-synucleinopathies;interfering amyloidogenesis pathways; Val-Gly-Gly-Ala-Thr-Thr-Thr-Gly-Val-Thr; multipole energies; spherical harmonics; extensions; particle mesh Ewald;

Abstract

It is well known that quantum computers are superior to classical computers in efficiently simulating quantum systems. The occurrence of quantum tunneling through a barrier, together with the oscillation of the state in potential wells, are clearly observed through the experimental results. This experiment has clearly demonstrated the possibility to observe and study profound physical phenomena within even the reach of small quantum computers. Quantum simulation is one of the most important aims of quantum computation ever since Feynman studied the likelihood of simulating one quantum system by another1. Recent years have witnessed fruitful results in the development of quantum computation, and it has been demonstrated that quantum computers can solve certain types of problems with a level of efficiency beyond the capability of classical computers2,3,4,5,6, among which the simulation of the dynamics of quantum systems is especially attractive because of the exponential improvement in computational resources and speeds. Quantum simulation has become a subject of intense investigation and has been realized in various situations, such as system evolution with a many-body interaction Hamiltonian7,8,9,10, the dynamics of entanglement11,12, quantum phase transitions13,14, and calculations of molecular properties15,16,17,18,19. Quantum tunneling plays an essential role in many quantum phenomena, such as the tunneling of superconducting Cooper pairs20 and alpha decay21. Moreover, tunneling has been widely applied in modern devices and modern experimental techniques, such as the tunnel diode22, the scanning tunneling microscope23 and so on. As a unique fundamental concept in quantum mechanics, the simulation of quantum tunneling is of great significance. Many important science problems, such as lattice quantum chromodynamics24, can be dealt with similarly. However due to the large number of quantum gates and qubits required, the simulation of quantum tunneling in a quantum computer has remained untested experimentally. Recently Sornborger25 proposed a digital simulation algorithm for demonstrating the tunneling of a particle in a double-well potential with no ancillary qubits, and at least halved the number of quantum gates. This makes it possible to simulate this important quantum effect in today’s quantum information processors with only a few qubits. Here we report the first experimental simulation of quantum tunneling through potential barriers, a widespread phenomenon of a unique quantum nature, via NMR techniques. Our experiment is based on a digital particle simulation algorithm and requires very few spin-1/2 nuclei without the need of ancillary qubits.In this paper, we report the first experimental digital quantum simulation of this significant quantum phenomenon via a liquid nuclear magnetic resonance (NMR) quantum information processor. In the experiment, the continuous process of one-dimensional tunneling of a particle through a potential barrier is clearly demonstrated, and the oscillation of the particle in potential wells is clearly observed. Our experiment has shown that with very few qubits, interesting quantum effects such as tunneling dynamics can be simulated with techniques which are within reach of current experimental simulation of quantum tunneling in small α-Synuclein aggregation simulated systems on Amyloid β-sheet helix-rich Val-Gly-Gly-Ala-Thr-Thr-Thr-Gly-Val-Thr peptide mimic modulators in α-synucleinopathy interfering amyloidogenesis quantum architectured pathways.

Keywords

Experimental simulation; quantum tunneling; small; α-Synuclein aggregation; simulated systems; Amyloid β-sheet; helix-rich; Val-Gly-Gly-Ala-Thr-Thr-Thr-Gly-Val-Thr; peptide mimic modulators; α-synucleinopathy; interfering; amyloidogenesis pathways;

Abstract

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. Our discussion, here, improves previously published argumentations very much whether Von Neumann’s Theory Meet al-Gly-Gly-Ala-Thr-Thr-Thr-Gly-Val-Thr peptide mimic modulators in α-synucleinopathy interfering amyloidogenesis Quantum Computated pathways.

Keywords

Von Neumann’s Theory; Meet; al-Gly-Gly-Ala-Thr-Thr-Thr-Gly-Val-Thr; peptide mimic; modulators; α-synucleinopathy; interfering amyloidogenesis; Quantum Computated; pathways; Quantum Measurement Theory, Quantum Computer, Formalism;Subject Areas; Applied Physics;

Abstract

Cavitation bubble collapse near rough solid wall is modeled by the multi- relaxation-time (MRT) pseudopotential lattice Boltzmann (LB) model. The modified forcing scheme, which can achieve LB model’s thermodynamic consistency by tuning a parameter related with the particle interaction range, is adopted to achieve desired stability and density ratio. The bubble collapse near rough solid wall was simulated by the improved MRT pseudopotential LB model. The mechanism of bubble collapse is studied by investigating the bubble profiles, pressure field and velocity field evolution. The eroding effects of collapsing bubble are analyzed in details. It is found that the process and the effect of the interaction between bubble collapse and rough solid wall are affected seriously by the geometry of solid boundary. At the same time, it demonstrates that the MRT pseudopotential LB model is a potential tool for the investigation of the interaction mechanism between the collapsing bubble and complex geometry Modeling boundaries for Collapsing al-Gly-Gly-Ala-Thr-Thr-Thr-Gly-Val-Thr peptide mimic modulators in α-synucleinopathy interfering amyloidogenesis Cavitations Bubble near Rough Solid Wall by Mulit-Relaxation-Time Pseudopotential Lattice Boltzmann Quantum Computated α-Synuclein aggregation simulated Model.

Keywords

Modeling for Collapsing; al-Gly-Gly-Ala-Thr-Thr-Thr-Gly-Val-Thr peptide mimic; modulators; α-synucleinopathy; interfering amyloidogenesis; Cavitations; Bubble; Rough; Solid Wall; Mulit-Relaxation-Time; Pseudopotential; Lattice Boltzmann; Quantum Computated; α-Synuclein; aggregation; simulated Model;

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. 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 efficient algorithms for multipole energies and derivatives based on spherical harmonics and extensions to 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 particle mesh Ewald pathways.

Keywords

Aggregation simulated studiesAmyloid β-sheet helix-richpeptide mimic modulators
α-Synuclein aggregationemerging templatedrug discoveryα-synucleinopathiesinterfering amyloidogenesis pathways

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. 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 efficient algorithms for multipole energies and derivatives based on spherical harmonics and extensions to 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 particle mesh Ewald pathways.

Keywords

Aggregation simulated studiesAmyloid β-sheet helix-richpeptide mimic modulators
α-Synuclein aggregationemerging templatedrug discoveryα-synucleinopathiesinterfering amyloidogenesis pathways

Abstract

Next-generation molecular force fields deliver accurate descriptions of non-covalent interactions by employing more elaborate functional forms than their predecessors. Much work has been dedicated to improving the description of the electrostatic potential (ESP) generated by these force fields. A common approach to improving the ESP is by augmenting the point charges on each center with higher-order multipole moments. The resulting anisotropy greatly improves the directionality of the non-covalent bonding, with a concomitant increase in computational cost. In this work, we develop an efficient strategy for enumerating multipole interactions, by casting an efficient spherical harmonic based approach within a particle mesh Ewald (PME) framework. Although the derivation involves lengthy algebra, the final expressions are relatively compact, yielding an approach that can efficiently handle both finite and periodic systems without imposing any approximations beyond PME. Forces and torques are readily obtained, making our method well suited to modern molecular dynamics simulations.Aggregation simulated studies on Ewald Aggregation simulated studies on an efficient algorithm for multipole energies and derivatives based on spherical harmonics and extensions to particle mesh 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

Ewald Aggregation, simulated studies, algorithm, multipole energies, spherical harmonics, extensions; particle mesh; Amyloid β-sheet helix-rich; Val-Gly-Gly-Ala-Thr-Thr-Thr-Gly-Val-Thr peptide mimic; modulators; α-Synuclein aggregation; emerging template; drug discovery; α-synucleinopathy; interfering amyloidogenesis pathways;

Abstract

An increased occurrence of aromatic residues in natural core sequences has led to widespread conclusions about the crucial role played by these residues in molecular recognition and self-assembly. Comparing the self-assembly of our fully aliphatic designed peptides with natural core sequences would also help to determine the significance and effect of π–π interactions on amyloid formation. The major hallmark of Parkinson’s disease (PD) is the progressive loss of dopaminergic neurons in the substantia nigra pars compacta, leading to the characteristic motor symptoms of resting tremors, bradykinesia and rigidity. The aim of the present study is to give a scaffolding hope recoring chemogenomic machine learning platform of the generation of innovative neuroprotective agents and improve their targetability to conserved binding short linear motif domains that are currently investigated for the treatment of PD in phase I-III clinical trials. The aim of the present study is aldo to in silico discover a gallic acid (GA) (3,4,5-trihydroxybenzoic acid), a benzoic acid derivative that belongs to a group of phenolic compounds known as phenolic acids by employing an array of biophysical. bioinformatic, chemicalinformatic and quantum molecular mechanics techniques to generate an α-syn fibrillation inhibitor to in silico disaggregate preformed α-syn amyloid fibrils. Additionally, by using structure activity relationship data obtained from fourteen structurally similar benzoic acid derivatives, it was determined that the inhibition of α-syn fibrillation by GA is related to the number of hydroxyl moieties and their position on the phenyl ring. GA may represent the starting point for designing new molecules that could be used for the treatment of PD and related disorders. It is well known that quantum computers are superior to classical computers in efficiently simulating quantum systems. Here we report the first experimental simulation of quantum tunneling through potential barriers, a widespread phenomenon of a unique quantum nature, via NMR techniques. Our experiment is based on a digital particle simulation algorithm and requires very few spin-1/2 nuclei without the need of ancillary qubits. The occurrence of quantum tunneling through a barrier, together with the oscillation of the state in potential wells, are clearly observed through the experimental results. This experiment has clearly demonstrated the possibility to observe and study profound physical phenomena within even the reach of small quantum computers challenging the importance of aromatic interactions in amyloidosis via aliphatic LD6(LAGD), ID3(IVD) and KE7(KLVFFAE) peptides, as a novel Experimental simulation of quantum tunneling in small GA-biophoric scaffolds for the generation of similar self-assembly chemico-lead molecules to amyloid core sequences.

Keywords

aromatic interactions; amyloidosis;aliphatic;extensively ultra;small peptides;novel biophoric; scaffold;computer-aided; imilar self-assembly;chemico-lead; molecules;amyloid core sequences;

Abstract

An increased occurrence of aromatic residues in natural core sequences has led to widespread conclusions about the crucial role played by these residues in molecular recognition and self-assembly. Comparing the self-assembly of our fully aliphatic designed peptides with natural core sequences would also help to determine the significance and effect of π–π interactions on amyloid formation. The major hallmark of Parkinson’s disease (PD) is the progressive loss of dopaminergic neurons in the substantia nigra pars compacta, leading to the characteristic motor symptoms of resting tremors, bradykinesia and rigidity. The aim of the present study is to give a scaffolding hope recoring chemogenomic machine learning platform of the generation of innovative neuroprotective agents and improve their targetability to conserved binding short linear motif domains that are currently investigated for the treatment of PD in phase I-III clinical trials. The aim of the present study is aldo to in silico discover a gallic acid (GA) (3,4,5-trihydroxybenzoic acid), a benzoic acid derivative that belongs to a group of phenolic compounds known as phenolic acids by employing an array of biophysical. bioinformatic, chemicalinformatic and quantum molecular mechanics techniques to generate an α-syn fibrillation inhibitor to in silico disaggregate preformed α-syn amyloid fibrils. Additionally, by using structure activity relationship data obtained from fourteen structurally similar benzoic acid derivatives, it was determined that the inhibition of α-syn fibrillation by GA is related to the number of hydroxyl moieties and their position on the phenyl ring. GA may represent the starting point for designing new molecules that could be used for the treatment of PD and related disorders. It is well known that quantum computers are superior to classical computers in efficiently simulating quantum systems. Here we report the first experimental simulation of quantum tunneling through potential barriers, a widespread phenomenon of a unique quantum nature, via NMR techniques. Our experiment is based on a digital particle simulation algorithm and requires very few spin-1/2 nuclei without the need of ancillary qubits. The occurrence of quantum tunneling through a barrier, together with the oscillation of the state in potential wells, are clearly observed through the experimental results. This experiment has clearly demonstrated the possibility to observe and study profound physical phenomena within even the reach of small quantum computers challenging the importance of aromatic interactions in amyloidosis via aliphatic LD6(LAGD), ID3(IVD) and KE7(KLVFFAE) peptides, as a novel Experimental simulation of quantum tunneling in small GA-biophoric scaffolds for the generation of similar self-assembly chemico-lead molecules to amyloid core sequences. Next-generation molecular force fields deliver accurate descriptions of non-covalent interactions by employing more elaborate functional forms than their predecessors. Much work has been dedicated to improving the description of the electrostatic potential (ESP) generated by these force fields. A common approach to improving the ESP is by augmenting the point charges on each center with higher-order multipole moments. The resulting anisotropy greatly improves the directionality of the non-covalent bonding, with a concomitant increase in computational cost. In this work, we develop an efficient strategy for enumerating multipole interactions, by casting an efficient spherical harmonic based approach within a particle mesh Ewald (PME) framework. Although the derivation involves lengthy algebra, the final expressions are relatively compact, yielding an approach that can efficiently handle both finite and periodic systems without imposing any approximations beyond PME. Forces and torques are readily obtained, making our method well suited to modern molecular dynamics simulations for multipole energies and derivatives based on spherical harmonics and extensions to particle mesh Ewald of aromatic interactions in amyloidosis via aliphatic LD6(LAGD), ID3(IVD) and KE7(KLVFFAE) peptides, as a novel Experimental simulation of quantum tunneling in small GA-biophoric scaffolds for the generation of similar self-assembly chemico-lead molecules to amyloid core sequences.

Keywords

aromatic interactions; amyloidosis;aliphatic;extensively ultra;small peptides;novel biophoric; scaffold;computer-aided; imilar self-assembly;chemico-lead; molecules;amyloid core sequences; efficient; algorithm;multipole energies; derivatives; spherical harmonics; extensions; particle mesh; Ewald;aromatic interactions;amyloidosis; aliphatic; LD6(LAGD), ID3(IVD) and KE7(KLVFFAE) peptides, Experimental simulation; quantum tunneling; ismall GA-biophoric scaffolds; similar self-assembly; chemico-lead molecules; amyloid core sequences;

Abstract

This paper deals with the some oscillation criteria for the two-dimensional neutral delay difference system of the form Examples of Oscillation and Asymptotic Behaviour of Solutions of Nonlinear Two-Dimensional Neutral Delay Difference Systems of aromatic interactions in amyloidosis via aliphatic LD6(LAGD), ID3(IVD) and KE7(KLVFFAE) peptides, as a novel Experimental simulation of quantum tunneling in small GA-biophoric scaffolds for the generation of similar self-assembly chemico-lead molecules to amyloid core sequences illustrating the results are inserted

Keywords

Asymptotic, Two-Dimensional Neutral Delay Difference Systems;Oscillation and Asymptotic Behaviour of Solutions; Nonlinear; Two-Dimensional; Neutral Delay; Difference Systems; aromatic interactions; amyloidosis; aliphatic; LD6(LAGD), ID3(IVD) and KE7(KLVFFAE) peptides, Experimental simulation; quantum tunneling; small GA-biophoric; scaffolds; self-assembly; chemico-lead; molecules; amyloid core sequences;