Conformation and internal mobility of 10,11-dihydro-5H-dibenzo[a,d]cycloheptene derivatives in solution. Conformational analysis of highly flexible structures

1988 ◽  
Vol 53 (17) ◽  
pp. 3988-3996 ◽  
Author(s):  
Walter Weissensteiner ◽  
Otmar Hofer ◽  
Ulrike G. Wagner
Keyword(s):  
Conformational Analysis ◽  
Flexible Structures ◽  
Internal Mobility

scholarly journals MICE-PES: An Algorithm for Accurate Conformational Analysis and its Implementation to Natural Products

2021 ◽  
Author(s):  
◽  
Muhammad Ali Hashmi
Keyword(s):  
Conformational Analysis ◽  
Degrees Of Freedom ◽  
Force Fields ◽  
Flexible Structures ◽  
Chemical Properties ◽  
General Purpose ◽  
Field Methods ◽  
Relative Configuration ◽  
Incremental Construction

<p>Secondary metabolites from natural sources have revolutionized the modern drug industry by acting as lead compounds. Many commercial drugs have evolved originally from natural molecules before being synthesized in the laboratory for commercialization. Because of the importance of natural molecules, it is crucial to determine their structural properties carefully as it is essential for their synthesis and studying their pharmacological behaviour. Many natural molecules have flexible structures and can adopt many different conformations in solution at room temperature. Hence, the determination of their relative configuration is a challenging task with the available experimental techniques. For structural analysis of natural molecules and to study their properties, all conformers which might be responsible for their chemical properties have to be considered.  Theoretical chemistry has been very helpful in absolute structure determination of complex and conformationally flexible natural molecules by calculating their theoretical nuclear magnetic resonance, ultraviolet, infra red, and circular dichroism spectra etc. There are a number of software tools that offer conformational analysis by utilizing different molecular mechanics approaches. They produce a large number of possible conformers and are not general purpose, thus compromising accuracy. Apart from that, different force fields available for conformational analysis and minimization have been designed for specific molecular classes and do not produce good results beyond their scope.  In the past, there have been reports about a “build-up procedure” for predicting the low energy conformations of peptides by optimising smaller fragments of the molecule under study and then joining them while minimizing their energies using force fields. Later on, this method was extended to predict the structure of DNA from sequences. This method used force field methods and did not gain much popularity due to its various limitations.  Here, MICE-PES (Method for the Incremental Construction and Exploration of the Potential Energy Surface) is presented, an algorithm which performs a conformational analysis using high level quantum chemical calculations by building the molecule incrementally from its smallest possible analogue whose conformational degrees of freedom are very well separated than the rest of the molecule. MICE-PES has been validated through studies on known biomolecule 3-epi-xestoaminol whose absolute configuration has been determined already by experimental and theoretical methods. MICE-PES has also been used to assign the relative configuration of a natural product (meroterphenol C) whose configuration could not be established experimentally. Overall, the development of MICE-PES will be very helpful in solving problems in the study of conformationally flexible systems, in all aspects of organic chemistry.</p>

scholarly journals MICE-PES: An Algorithm for Accurate Conformational Analysis and its Implementation to Natural Products

2021 ◽  
Author(s):  
◽  
Muhammad Ali Hashmi
Keyword(s):  
Conformational Analysis ◽  
Degrees Of Freedom ◽  
Force Fields ◽  
Flexible Structures ◽  
Chemical Properties ◽  
General Purpose ◽  
Field Methods ◽  
Relative Configuration ◽  
Incremental Construction

<p>Secondary metabolites from natural sources have revolutionized the modern drug industry by acting as lead compounds. Many commercial drugs have evolved originally from natural molecules before being synthesized in the laboratory for commercialization. Because of the importance of natural molecules, it is crucial to determine their structural properties carefully as it is essential for their synthesis and studying their pharmacological behaviour. Many natural molecules have flexible structures and can adopt many different conformations in solution at room temperature. Hence, the determination of their relative configuration is a challenging task with the available experimental techniques. For structural analysis of natural molecules and to study their properties, all conformers which might be responsible for their chemical properties have to be considered.  Theoretical chemistry has been very helpful in absolute structure determination of complex and conformationally flexible natural molecules by calculating their theoretical nuclear magnetic resonance, ultraviolet, infra red, and circular dichroism spectra etc. There are a number of software tools that offer conformational analysis by utilizing different molecular mechanics approaches. They produce a large number of possible conformers and are not general purpose, thus compromising accuracy. Apart from that, different force fields available for conformational analysis and minimization have been designed for specific molecular classes and do not produce good results beyond their scope.  In the past, there have been reports about a “build-up procedure” for predicting the low energy conformations of peptides by optimising smaller fragments of the molecule under study and then joining them while minimizing their energies using force fields. Later on, this method was extended to predict the structure of DNA from sequences. This method used force field methods and did not gain much popularity due to its various limitations.  Here, MICE-PES (Method for the Incremental Construction and Exploration of the Potential Energy Surface) is presented, an algorithm which performs a conformational analysis using high level quantum chemical calculations by building the molecule incrementally from its smallest possible analogue whose conformational degrees of freedom are very well separated than the rest of the molecule. MICE-PES has been validated through studies on known biomolecule 3-epi-xestoaminol whose absolute configuration has been determined already by experimental and theoretical methods. MICE-PES has also been used to assign the relative configuration of a natural product (meroterphenol C) whose configuration could not be established experimentally. Overall, the development of MICE-PES will be very helpful in solving problems in the study of conformationally flexible systems, in all aspects of organic chemistry.</p>

Progress in high-resolution CRYO-SEM imaging of viral particles

1996 ◽  
Vol 54 ◽  
pp. 818-819
Author(s):  
Ya Chen ◽  
Geoffrey Letchworth ◽  
John White
Keyword(s):  
Electron Microscopy ◽  
Scanning Electron Microscopy ◽  
High Resolution ◽  
Structural Information ◽  
Signal To Noise Ratio ◽  
Flexible Structures ◽  
Simian Virus ◽  
Topographic Features ◽  
Viral Particles ◽  
Scanning Electron

Low-temperature high-resolution scanning electron microscopy (cryo-HRSEM) has been successfully utilized to image biological macromolecular complexes at nanometer resolution. Recently, imaging of individual viral particles such as reovirus using cryo-HRSEM or simian virus (SIV) using HRSEM, HV-STEM and AFM have been reported. Although conventional electron microscopy (e.g., negative staining, replica, embedding and section), or cryo-TEM technique are widely used in studying of the architectures of viral particles, scanning electron microscopy presents two major advantages. First, secondary electron signal of SEM represents mostly surface topographic features. The topographic details of a biological assembly can be viewed directly and will not be obscured by signals from the opposite surface or from internal structures. Second, SEM may produce high contrast and signal-to-noise ratio images. As a result of this important feature, it is capable of visualizing not only individual virus particles, but also asymmetric or flexible structures. The 2-3 nm resolution obtained using high resolution cryo-SEM made it possible to provide useful surface structural information of macromolecule complexes within cells and tissues. In this study, cryo-HRSEM is utilized to visualize the distribution of glycoproteins of a herpesvirus.

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