Abstract

Background

Molecular Mechanics (MM) is the method of choice for computational studies of biomolecular systems owing to its modest computational cost, which makes it possible to routinely perform molecular dynamics (MD) simulations on chemical systems of biophysical and biomedical relevance.

Scope of Review

As one of the main factors limiting the accuracy of MD results is the empirical force field used, the present paper offers a review of recent developments in the CHARMM additive force field, one of the most popular bimolecular force fields. Additionally, we present a detailed discussion of the CHARMM Drude polarizable force field, anticipating a growth in the importance and utilization of polarizable force fields in the near future. Throughout the discussion emphasis is placed on the force fields’ parametrization philosophy and methodology.

Major Conclusions

Recent improvements in the CHARMM additive force field are mostly related to newly found weaknesses in the previous generation of additive force fields. Beyond the additive approximation is the newly available CHARMM Drude polarizable force field, which allows for MD simulations of up to 1 microsecond on proteins, DNA, lipids and carbohydrates.

General Significance

Addressing the limitations ensures the reliability of the new CHARMM36 additive force field for the types of calculations that are presently coming into routine computational reach while the availability of the Drude polarizable force fields offers a model that is an inherently more accurate model of the underlying physical forces driving macromolecular structures and dynamics.

Keywords

molecular dynamics, empirical force field, potential energy function, molecular mechanics, computer-aided drug design, biophysics

Abstract

The quantum stochastic differential equation derived from the Lindblad form quantum master equation is investigated. The general formulation in terms of environment operators representing the quantum state diffusion is given. The numerical simulation algorithm of stochastic process of direct photodetection of a driven two-level system for the predictions of the dynamical behavior is proposed. The effectiveness and superiority of the algorithm are verified by the performance analysis of the accuracy and the computational cost in comparison with the classical Runge-Kutta algorithm.Simulation of Quantum Dynamics Based on the Quantum Stochastic Differential EquationAn 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. 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 Simulation of Quantum Dynamics Based on the Quantum Stochastic Differential Equation 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

RRT-based; algorithm;high-resolution; refinement;binding affinity; estimation;peptide inhibitors;In silico discovery; high resolution;docking; refinement;conserved peptide; substitution;mimetic; pharmacostructure;suppressor; VEGFR-3; Simulation of Quantum Dynamics; Quantum Stochastic; Differential Equation; algorithm for high-resolution refinement;

Abstract

Background

Molecular Mechanics (MM) is the method of choice for computational studies of biomolecular systems owing to its modest computational cost, which makes it possible to routinely perform molecular dynamics (MD) simulations on chemical systems of biophysical and biomedical relevance.

Scope of Review

As one of the main factors limiting the accuracy of MD results is the empirical force field used, the present paper offers a review of recent developments in the CHARMM additive force field, one of the most popular bimolecular force fields. Additionally, we present a detailed discussion of the CHARMM Drude polarizable force field, anticipating a growth in the importance and utilization of polarizable force fields in the near future. Throughout the discussion emphasis is placed on the force fields’ parametrization philosophy and methodology.

General Significance

Addressing the limitations ensures the reliability of the new CHARMM36 additive force field for the types of calculations that are presently coming into routine computational reach while the availability of the Drude polarizable force fields offers a model that is an inherently more accurate model of the underlying physical forces driving macromolecular structures and dynamics.

Major Conclusions

Recent improvements in the CHARMM additive force field are mostly related to newly found weaknesses in the previous generation of additive force fields. Beyond the additive approximation is the newly available CHARMM Drude polarizable force field, which allows for MD simulations of CHARMM additive polarizable force fields for biophysics computer-aided drug design algorithms 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

molecular dynamics, empirical force field, potential energy function, molecular mechanics, computer-aided drug design, biophysics; CHARMM additive; polarizable force fields; biophysics; computer-aided drug design; algorithms; high-resolution refinement; binding affinity; estimation of inhibitors; CGQMCTVWCSSGC targeted; conserved peptide; substitution; mimetic pharmacostructures; VEGFR-3-mediated; oncogenic effects

Abstract

The main facts about the scale of time considered as a plot of a sequence of events are submitted both to a review and a more detailed calculation. Classical progressive character of the time variable, present in the everyday life and in the modern science, too, is compared with a circular-like kind of advancement of time. This second kind of the time behaviour can be found suitable when a perturbation process of a quantum-mechanical system is examined. In fact the paper demonstrates that the complicated high-order Schrödinger perturbation energy of a non-degenerate quantum state becomes easy to approach of the basis of Circular Scale of Time and Energy of a Quantum State Calculated from the Schrödinger Perturbation Theory for high-resolution refinement and binding affinity estimation of inhibitors of CGQMCTVWCSSGC targeted conserved peptide substitution mimetic pharmacostructures antagonizing VEGFR-3-mediated oncogenic effects. For example for the perturbation order N = 20 instead of 19! ≈ 1.216 × 1017 Feynman diagrams, the contribution of which should be derived and calculated, only less than 218 ≈ 2.621 × 105 terms belonging to N = 20 should be taken into account to the same purpose.

Keywords

Circular Scale of Time, Schrödinger Perturbation Theory, Non-Degenerate Quantum State;Circular Scale; Time and Energy; Quantum State; Schrödinger Perturbation; Theory for high-resolution refinement; binding affinity; inhibitors; CGQMCTVWCSSGC targeted; conserved peptide; substitution mimetic; pharmacostructures; antagonizing VEGFR-3;mediated oncogenic effects.

Abstract

Background

Molecular Mechanics (MM) is the method of choice for computational studies of biomolecular systems owing to its modest computational cost, which makes it possible to routinely perform molecular dynamics (MD) simulations on chemical systems of biophysical and biomedical relevance.

Scope of Review

As one of the main factors limiting the accuracy of MD results is the empirical force field used, the present paper offers a review of recent developments in the CHARMM additive force field, one of the most popular bimolecular force fields. Additionally, we present a detailed discussion of the CHARMM Drude polarizable force field, anticipating a growth in the importance and utilization of polarizable force fields in the near future. Throughout the discussion emphasis is placed on the force fields’ parametrization philosophy and methodology.

Major Conclusions

Recent improvements in the CHARMM additive force field are mostly related to newly found weaknesses in the previous generation of additive force fields. Beyond the additive approximation is the newly available CHARMM Drude polarizable force field, which allows for MD simulations of up to 1 microsecond on proteins, DNA, lipids and carbohydrates.

General Significance

Addressing the limitations ensures the reliability of the new CHARMM36 additive force field for the types of calculations that are presently coming into routine computational reach while the availability of the Drude polarizable force fields offers a model that is an inherently more accurate model of the underlying physical forces driving macromolecular structures and dynamics.

Keywords

algorithm estimation; CHARMM additive; polarizable force fields; biophysics; computer-aided drug design; high-resolution refinement; high binding affinity; inhibitors; CGQMCTVWCSSGC targeted; conserved peptide; substitution mimetic; pharmacostructures; VEGFR-3-mediated; oncogenic effects;

Abstract

Diabetes mellitus affects over 100 million individuals worldwide. In the U.S., the estimated healthcare costs of those affected by diabetes is approximately 136 billion dollars annually. Diabetes mellitus is a disorder of the metabolism that is characterized by the inability of the pancreas to secrete sufficient amounts of insulin, which results in large fluctuations in blood glucose levels and can have both short- and long-term physiological consequences. Glucagon-like peptide-1 (7-36) amide (GLP-1) is a gut hormone, released postprandially,which stimulates insulin secretion and insulin gene expression as well as pancreatic B-cell growth. Together with glucose-dependent insulinotropic polypeptide (GIP), it is responsible for the incretin effect which is the augmentation of insulin secretion following oral administration of glucose. We therefore for the first time provided in this scientific project a promising alternative to bridge the knowledge gap between insulinotropic biological conserved signaling pathways and chemistry informatic tools which significantly boost the productivity of our chemogenomics research for the distribution of quantum Fisher information in asymmetric cloning computational target fishing mining machinery as an identification tool for predicting therapeutic potential of GLP-1, INGAP-P and IGLHDPSHGTLPNGS peptide mimetic insulinotropic of high-potency compounds based on chemogenomic databases.

Keywords

computational; target fishing; mining machinery;novel target; Identification tool;predicting therapeutic; proinsulin; GLP-1; INGAP-Ppeptide; mimetic;insulinotropic; compounds;chemogenomic;database,Distribution; quantum; Fisher; information; asymmetric; cloning machines;

Abstract

An unknown quantum state cannot be copied and broadcast freely due to the no-cloning theorem. Approximate cloning schemes have been proposed to achieve the optimal cloning characterized by the maximal fidelity between the original and its copies. Here, from the perspective of quantum Fisher information (QFI), we investigate the distribution of QFI in asymmetric cloning machines which produce two nonidentical copies. As one might expect, improving the QFI of one copy results in decreasing the QFI of the other copy. It is perhaps also unsurprising that asymmetric phase-covariant cloning outperforms universal cloning in distributing QFI since a priori information of the input state has been utilized. However, interesting results appear when we compare the distributabilities of fidelity (which quantifies the full information of quantum states), and QFI (which only captures the information of relevant parameters) in asymmetric cloning machines. Unlike the results of fidelity, where the distributability of symmetric cloning is always optimal for any d-dimensional cloning, we find that any asymmetric cloning outperforms symmetric cloning on the distribution of QFI for d ≤ 18, whereas some but not all asymmetric cloning strategies could be worse than symmetric ones when d > 18. Classical information can be replicated perfectly and broadcast without fundamental limitations. However, information encoded in quantum states is subject to several intrinsic restrictions of quantum mechanics, such as Heisenberg’s uncertainty relations1 and quantum no-cloning theorem2. The no-cloning theorem tells us that an unknown quantum state cannot be perfectly replicated because of the linearity of the time evolution in quantum physics, which is the essential prerequisite for the absolute security of quantum cryptography3. Nevertheless, it is still possible to clone a quantum state approximately, or instead, clone it perfectly with certain probability4,5 distributions of a computational target fishing mining quantum Fisher information in asymmetric cloning machinery as an Identification tool for predicting therapeutic potential of GLP-1, INGAP-P and IGLHDPSHGTLPNGS peptide mimetic insulinotropic of high-potency compounds based on chemogenomic databases.

Keywords

Distribution of quantum; Fisher information; asymmetric cloning machines; computational target fishing; mining machinery; Identification tool; predicting therapeutic; GLP-1, INGAP-P; IGLHDPSHGTLPNGS peptide; mimetic insulinotropic; high-potency; chemogenomic databases;

Abstract

The main facts about the scale of time considered as a plot of a sequence of events are submitted both to a review and a more detailed calculation. Classical progressive character of the time variable, present in the everyday life and in the modern science, too, is compared with a circular-like kind of advancement of time. This second kind of the time behaviour can be found suitable when a perturbation process of a quantum-mechanical system is examined. In fact the paper demonstrates that the complicated high-order Schrödinger perturbation energy of a non-degenerate quantum state becomes easy to approach of the basis of a circular scale. For example for the perturbation order N = 20 instead of 19! ≈ 1.216 × 1017 Feynman diagrams, the contribution of which should be derived and calculated, only less than 218 ≈ 2.621 × 105 terms belonging to N = 20 should be taken into account to the same purpose of Circular Scale of Time and Energy of a Quantum State Calculated from the Schrödinger Perturbation Theory as an identification tool for predicting therapeutic potential of GLP-1, INGAP-P and IGLHDPSHGTLPNGS peptide mimetic insulinotropic of high-potency compounds based on chemogenomic databases.

Keywords

Circular Scale of Time, Schrödinger Perturbation Theory, Non-Degenerate Quantum State; Circular Scale of Time; Energy of a Quantum State; Schrödinger Perturbation Theory; identification tool; GLP-1, INGAP-P;IGLHDPSHGTLPNGS peptide mimetic; insulinotropic; high-potency; compounds; chemogenomic databases;

Abstract

An unknown quantum state cannot be copied and broadcast freely due to the no-cloning theorem. Approximate cloning schemes have been proposed to achieve the optimal cloning characterized by the maximal fidelity between the original and its copies. Here, from the perspective of quantum Fisher information (QFI), we investigate the distribution of QFI in asymmetric cloning machines which produce two nonidentical copies. As one might expect, improving the QFI of one copy results in decreasing the QFI of the other copy. It is perhaps also unsurprising that asymmetric phase-covariant cloning outperforms universal cloning in distributing QFI since a priori information of the input state has been utilized. However, interesting results appear when we compare the distributabilities of fidelity (which quantifies the full information of quantum states), and QFI (which only captures the information of relevant parameters) in asymmetric cloning machines. Unlike the results of fidelity, where the distributability of symmetric cloning is always optimal for any d-dimensional cloning, we find that any asymmetric cloning outperforms symmetric cloning on the distribution of QFI for d ≤ 18, whereas some but not all asymmetric cloning strategies could be worse than symmetric ones when d > 18. Classical information can be replicated perfectly and broadcast without fundamental limitations. However, information encoded in quantum states is subject to several intrinsic restrictions of quantum mechanics, such as Heisenberg’s uncertainty relations1 and quantum no-cloning theorem2. The no-cloning theorem tells us that an unknown quantum state cannot be perfectly replicated because of the linearity of the time evolution in quantum physics, which is the essential prerequisite for the absolute security of quantum cryptography3. Nevertheless, it is still possible to clone a quantum state approximately, or instead, clone it perfectly with certain probability4,5 distributions of a computational target fishing mining quantum Fisher information in asymmetric cloning machinery as an Identification tool for predicting therapeutic potential of GLP-1, INGAP-P and IGLHDPSHGTLPNGS peptide mimetic insulinotropic of high-potency compounds based on chemogenomic databases.

Keywords

Distribution of quantum; Fisher information; asymmetric cloning machines; computational target fishing; mining machinery; Identification tool; predicting therapeutic; GLP-1, INGAP-P; IGLHDPSHGTLPNGS peptide; mimetic insulinotropic; high-potency; chemogenomic databases

Abstract

The main facts about the scale of time considered as a plot of a sequence of events are submitted both to a review and a more detailed calculation. Classical progressive character of the time variable, present in the everyday life and in the modern science, too, is compared with a circular-like kind of advancement of time. This second kind of the time behaviour can be found suitable when a perturbation process of a quantum-mechanical system is examined. In fact the paper demonstrates that the complicated high-order Schrödinger perturbation energy of a non-degenerate quantum state becomes easy to approach of the basis of a circular scale. For example for the perturbation order N = 20 instead of 19! ≈ 1.216 × 1017 Feynman diagrams, the contribution of which should be derived and calculated, only less than 218 ≈ 2.621 × 105 terms belonging to N = 20 should be taken into account to the same purpose of Circular Scale of Time and Energy of a Quantum State Calculated from the Schrödinger Perturbation Theory as an identification tool for predicting therapeutic potential of GLP-1, INGAP-P and IGLHDPSHGTLPNGS peptide mimetic insulinotropic of high-potency compounds based on chemogenomic databases.

Keywords

Circular Scale of Time, Schrödinger Perturbation Theory, Non-Degenerate Quantum State; Circular Scale of Time; Energy of a Quantum State; Schrödinger Perturbation Theory; identification tool; GLP-1, INGAP-P;IGLHDPSHGTLPNGS peptide mimetic; insulinotropic; high-potency; compounds; chemogenomic databases;