Low-energy conformers

These programs generate one low-energy conformation for each molecule. 

Pharmacophore keys Family of low-energy conformations See Section 12.9.4... 

Conformation search techniques can be used to find very-low-energy conformations, which are most relevant to polymers that will be given a long annealing time. 

Polymers can be crystalline, but may not be easy to crystallize. Computational studies can be used to predict whether a polymer is likely to crystallize readily. One reason polymers fail to crystallize is that there may be many conformers with similar energies and thus little thermodynamic driving force toward an ordered conformation. Calculations of possible conformations of a short oligomer can be used to determine the difference in energy between the most stable conformer and other low-energy conformers. 

For a conformation in a relatively deep local minimum, a room temperature molecular dynamics simulation may not overcome the barrier and search other regions of conformational space in reasonable computing time. To overcome barriers, many conformational searches use elevated temperatures (600-1200 K) at constant energy. To search conformational space adequately, run simulations of 0.5-1.0 ps each at high temperature and save the molecular structures after each simulation. Alternatively, take a snapshot of a simulation at about one picosecond intervals to store the structure. Run a geometry optimization on each structure and compare structures to determine unique low-energy conformations. 

A molecular dynamics simulation used for a conformational search can provide a quick assessment of low energy conformers suitable for further analysis. Plot the average potential energy of the molecule at each geometry. This plot may also suggest conformational changes in a molecule. 

To extract the conformational properties of the molecule that is being studied, the conformational ensemble that was sampled and optimized must be analyzed. The analysis may focus on global properties, attempting to characterize features such as overall flexibility or to identify common trends in the conformation set. Alternatively, it may be used to identify a smaller subset of characteristic low energy conformations, which may be used to direct future drug development efforts. It should be stressed that the different conformational analysis tools can be applied to any collection of molecular conformations. These... 

Figure 2 A low energy conformation of a 27 mer lattice model on a 3 X 3 X 3 cubic lattice. (Adapted from Ref. 11.)...

The replacement of carbon by other elements produces changes in several structural parameters and consequently affects the conformational characteristics of the molecule. In this section, we will first describe some stereochemical features of heterocyclic analogs of cycloalkanes. For the purpose of elaborating conformational principles, the discussion will focus on six-membered rings, so that the properties may be considered in the context of a ring system possessing a limited number of low-energy conformations. 

Analyze the low-energy conformers of trans-2-methylcyclohexyl tosylate in the same way. What alkenes will be obtained from the trans tosylate ... 

Molecules of this complexity typically exist as a collection of many different conformers, and those shown should only be taken as representative (low-energy) conformers. 

A set of low-energy conformers has been provided for alanine (R=CH3) tetramer (terminated at both ends by amide functionality). For each conformer, identify each of the a carbons and measure the (j) and v(/ dihedral angles (see table below). 

It is unrealistic to expect that any single conformer of a polymer will adequately represent the overall size and shape of the polymer. The low-energy conformer for each polymer strand shown here is merely meant to allow identification of the polymer in terms of its components. 

Fig. 2.19 Comparison of the 12- and 10-membered turns found in the 12/10-helix of 72 together with corresponding backbone di- hedral angles. The angles were extracted from the low energy conformer of 72 depicted in Fig. 2.18 and based on NMR data...

Fig. 2.31 Comparison of the turn segment found in hairpin 122 with a naturally-occuring type II / -turn of a-polypeptides together with backbone dihedral angles in degrees. In the case of 122, the angles were extracted from one low energy conformer derived from NMR data and shown in Fig. 2.30. Torsion angles with comparable values are shown in bold [191, 195]...

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