Introduction

2003 ◽  
Keyword(s):  
Molecular Dynamics ◽  
Computational Chemistry ◽  
Mathematical Theory ◽  
Fundamental Equation ◽  
Point Of View ◽  
Scaling Relations ◽  
Approximate Methods ◽  
Computational Speed ◽  
Diverse Field ◽  
Physical Laws

Molecular dynamics deals with the motion of and the reaction between atoms and molecules. The fundamental theory for the description of essentially all aspects of the area has been known and defined through the non-relativistic Schrdinger equation since 1926. The “only” problem, therefore, is the solution of this fundamental equation. Unfortunately, this solution is not straightforward and, as early as 1929, prompted the following remark by Dirac (1929). . . The underlying physical laws necessary for the mathematical theory of a large part of physics and the whole of chemistry are thus completely known, and the difficulty is only that the application of these laws leads to equations much too complicated to be soluble. . . . Dirac could, for that matter, have added the area of molecular biochemistry. But here the systems become even bigger and therefore the above statement is even more correct. What neither Dirac nor anybody else at that time could foresee was the invention of the computer. With that, a whole new area, namely that of computational chemistry, was created. The recent five-volume work Encyclopedia of Computational Chemistry (1998[1]), with several hundred entries, bears witness to the tremendous evolution in this particular area over the last fifty years or so. The success of computational chemistry has to do not only with computers and the increase in computational speed but also with the development of new methods. Here again it should be emphasized that the availability of computers makes the construction of approximate methods a very rich and diverse field with many possibilities. Thus, this combination of computer power and the invention of theoretical and computational methods has changed the pessimistic point of view into an optimistic one. To quote Clementi (1972), “We can calculate everything.” Although this statement, at least in 1972, was somewhat optimistic, development since then has shown that the attitude should be quite optimistic. The purpose of approximate methods should be, and always is, to try to circumvent the bad scaling relations of quantum mechanics.

Design of Inhibitors for Glyceraldehyde-3-phosphate Dehydrogenase (GAPDH) Enzyme of Leishmania mexicana

2020 ◽  
Vol 16 (6) ◽  
pp. 784-795
Author(s):  
Krisnna M.A. Alves ◽  
Fábio José Bonfim Cardoso ◽  
Kathia M. Honorio ◽  
Fábio A. de Molfetta
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
Binding Site ◽  
Point Of View ◽  
New Drugs ◽  
Leishmania Mexicana ◽  
Receptor Complexes ◽  
Starting Point ◽  
Dynamics Simulations ◽  
Selection Of

Background:: Leishmaniosis is a neglected tropical disease and glyceraldehyde 3- phosphate dehydrogenase (GAPDH) is a key enzyme in the design of new drugs to fight this disease. Objective:: The present study aimed to evaluate potential inhibitors of GAPDH enzyme found in Leishmania mexicana (L. mexicana). Methods: A search for novel antileishmanial molecules was carried out based on similarities from the pharmacophoric point of view related to the binding site of the crystallographic enzyme using the ZINCPharmer server. The molecules selected in this screening were subjected to molecular docking and molecular dynamics simulations. Results:: Consensual analysis of the docking energy values was performed, resulting in the selection of ten compounds. These ligand-receptor complexes were visually inspected in order to analyze the main interactions and subjected to toxicophoric evaluation, culminating in the selection of three compounds, which were subsequently submitted to molecular dynamics simulations. The docking results showed that the selected compounds interacted with GAPDH from L. mexicana, especially by hydrogen bonds with Cys166, Arg249, His194, Thr167, and Thr226. From the results obtained from molecular dynamics, it was observed that one of the loop regions, corresponding to the residues 195-222, can be related to the fitting of the substrate at the binding site, assisting in the positioning and the molecular recognition via residues responsible for the catalytic activity. Conclusion:: he use of molecular modeling techniques enabled the identification of promising compounds as inhibitors of the GAPDH enzyme from L. mexicana, and the results obtained here can serve as a starting point to design new and more effective compounds than those currently available.

On the displacements of the contours of the optic-electronic space images. Mathematical modeling of displacement

2017 ◽  
Vol 992 (4) ◽  
pp. 32-38 ◽  
Author(s):  
E.G. Voronin
Keyword(s):  
Mathematical Modeling ◽  
Remote Sensing ◽  
Mathematical Model ◽  
Point Of View ◽  
Design Features ◽  
Space Images ◽  
Electronic Imaging ◽  
Measuring Accuracy ◽  
Physical Laws

The article opens a cycle of three consecutive publications dedicated to the phenomenon of the displacement of the same points in overlapping scans obtained adjacent CCD matrices with opto-electronic imagery. This phenomenon was noticed by other authors, but the proposed explanation for the origin of displacements and the resulting estimates are insufficient, and developed their solutions seem controversial from the point of view of recovery of the measuring accuracy of opticalelectronic space images, determined by the physical laws of their formation. In the first article the mathematical modeling of the expected displacements based on the design features of a scanning opto-electronic imaging equipment. It is shown that actual bias cannot be forecast, because they include additional terms, which may be gross, systematic and random values. The proposed algorithm for computing the most probable values of the additional displacement and ways to address some of the systematic components of these displacements in a mathematical model of optical-electronic remote sensing.

scholarly journals On the Use of the Discrete Constant pH Molecular Dynamics to Describe the Conformational Space of Peptides

Polymers ◽  
2020 ◽  
Vol 13 (1) ◽  
pp. 99
Author(s):  
Cristian Privat ◽  
Sergio Madurga ◽  
Francesc Mas ◽  
Jaime Rubio-Martínez
Keyword(s):  
Molecular Dynamics ◽  
Amino Acids ◽  
Md Simulations ◽  
Point Of View ◽  
Conformational Space ◽  
Conformational Sampling ◽  
Protonation State ◽  
Constant Ph ◽  
Biochemical Systems ◽  
Constant Ph Molecular Dynamics

Solvent pH is an important property that defines the protonation state of the amino acids and, therefore, modulates the interactions and the conformational space of the biochemical systems. Generally, this thermodynamic variable is poorly considered in Molecular Dynamics (MD) simulations. Fortunately, this lack has been overcome by means of the Constant pH Molecular Dynamics (CPHMD) methods in the recent decades. Several studies have reported promising results from these approaches that include pH in simulations but focus on the prediction of the effective pKa of the amino acids. In this work, we want to shed some light on the CPHMD method and its implementation in the AMBER suitcase from a conformational point of view. To achieve this goal, we performed CPHMD and conventional MD (CMD) simulations of six protonatable amino acids in a blocked tripeptide structure to compare the conformational sampling and energy distributions of both methods. The results reveal strengths and weaknesses of the CPHMD method in the implementation of AMBER18 version. The change of the protonation state according to the chemical environment is presumably an improvement in the accuracy of the simulations. However, the simulations of the deprotonated forms are not consistent, which is related to an inaccurate assignment of the partial charges of the backbone atoms in the CPHMD residues. Therefore, we recommend the CPHMD methods of AMBER program but pointing out the need to compare structural properties with experimental data to bring reliability to the conformational sampling of the simulations.

scholarly journals Conformational energies and equilibria of cyclic dinucleotides in vacuo and in solution: computational chemistry vs. NMR experiments

2021 ◽  
Author(s):  
Ondrej Gutten ◽  
Petr Jurečka ◽  
Zahra Aliakbar Tehrani ◽  
Miloš Buděšínský ◽  
Jan Řezáč ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Quantum Mechanics ◽  
Computational Chemistry ◽  
Computational Error ◽  
Cyclic Dinucleotides ◽  
Error Bars ◽  
Conformational Energies

Computational “error bars” for modelling cyclic dinucleotides – NMR experiment vs. quantum mechanics and molecular dynamics.

Reasons, Causes, and Intentional Explanation

1986 ◽  
Vol 8 (1) ◽  
Author(s):  
Frederick Stoutland
Keyword(s):  
Social Sciences ◽  
Human Behavior ◽  
Point Of View ◽  
The Social ◽  
Intentional Explanation ◽  
Covering Law ◽  
Causal Laws ◽  
Physical Laws ◽  
And Behavior

AbstractThe reasons-causes debate concerns whether explanations of human behavior in terms of an agent's reasons presuppose causal laws. This paper considers three approaches to this debate: the covering law model which holds that there are causal laws covering both reasons and behavior, the intentionalist approach which denies any role to causal laws, and Donald Davidson’s point of view which denies that causal laws connect reasons and behavior, but holds that reasons and behavior must be covered by physical laws if reasons explanations are to be valid. I defend the intentionalist approach against the two causalist approaches and conclude with reflections on the significance of the debate for the social sciences.

Excess Streamwise Vorticity and Its Role in Secondary Flow

1987 ◽  
Vol 201 (6) ◽  
pp. 413-420 ◽  
Author(s):  
P W James
Keyword(s):  
Secondary Flow ◽  
Gas Turbines ◽  
Three Dimensional ◽  
Point Of View ◽  
Streamwise Vorticity ◽  
Three Dimensional Flow ◽  
Approximate Methods ◽  
Blade Row ◽  
Flow Through ◽  
Loss Term

The purpose of this paper is, firstly, to show how the concept of excess secondary vorticity arises naturally from attempts to recover three-dimensional flow details lost in passage-averaging the equations governing the flow through gas turbines. An equation for the growth of excess streamwise vorticity is then derived. This equation, which allows for streamwise entropy gradients through a prescribed loss term, could be integrated numerically through a blade-row to provide the excess vorticity at the exit to a blade-row. The second part of the paper concentrates on the approximate methods of Smith (1) and Came and Marsh (2) for estimating this quantity and demonstrates their relationship to each other and to the concept of excess streamwise vorticity. Finally the relevance of the results to the design of blading for gas turbines, from the point of view of secondary flow, is discussed.

The Aiming Problem in Aerial Gunnery

1957 ◽  
Vol 8 (1) ◽  
pp. 31-48
Author(s):  
M. Hancock
Keyword(s):  
Sufficient Accuracy ◽  
Point Of View ◽  
Complete Analysis ◽  
Mathematical Treatment ◽  
Approximate Methods ◽  
Simplified Analysis ◽  
Points Of View ◽  
Comparison Of The Results

SummaryThe aiming problem in aerial gunnery has formerly been analysed by approximate methods which allow results of sufficient accuracy for practical requirements to be obtained from a very simple mathematical treatment. There has therefore been no practical demand for any more elaborate analysis, although the development of a more exact treatment of the problem is not without interest from the academic point of view. In this paper a more complete analysis is developed in a form which is generally applicable to a broader class of aiming problems. The relevant parts of the standard external ballistic analysis for projectiles fired from guns are also included for the sake of completeness, and the earlier simplified analysis of the aiming problem is also presented to allow comparison of the results with those of the more complete analysis. Finally, a section on the gunner's view of the aiming problem is included, to provide an explanation of certain difficulties which frequently arise through neglect of the important differences between the points of view of an observer moving with the gun and an observer at rest in the air.

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