Conformation properties

There are two problems to consider when calculating 3D pharmacophores. First, unless the molecules are all completely rigid, one must take account of their conformational properties The second problem is to determine which combinations of pharmacophoric groups are common to the molecules and can be positioned in a similar orientation in space. More than one pharmacophore may be possible indeed, some algorithms can generate hundreds of possible pharmacophores, which must then be evaluated to determine which best fits the data. It is important to realise that all of these approaches to finding 3D pharmacophores assume that all of the molecules bind in a common manner to the macromolecule. 

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... 

In the next section we describe the basic models that have been used in simulations so far and summarize the Monte Carlo and molecular dynamics techniques that are used. Some principal results from the scaling analysis of EP are given in Sec. 3, and in Sec. 4 we focus on simulational results concerning various aspects of static properties the MWD of EP, the conformational properties of the chain molecules, and their behavior in constrained geometries. The fifth section concentrates on the specific properties of relaxation towards equilibrium in GM and LP as well as on the first numerical simulations of transport properties in such systems. The final section then concludes with summary and outlook on open problems. 

Generally, the models used for simulation of living polymers can be divided roughly into two classes, focused on static or dynamic properties of the LP or GM. The static models are mainly designed to study equilibrium conformational properties of the polymer chains, critical behavior at the polymerization transition, and molecular weight distribution... 

Examine the structure of cyclodecane, a molecule which contains the same number of carbons as decalin, but only has one ring (a model of the most stable conformation is provided). Compare it to cis and trans decalin. Make a plastic model of cyclodecane. Is it flexible or locked What conformational properties of cyclodecane can be anticipated from the properties of decalins What properties cannot be anticipated How do you account for this ... 

Conformational properties of DNA strands containing guanine and adenine 98CLY530. 

The conformational properties of medium and large ring organic molecules have profound consequences on the stereochemical course of dimethylcuprate addition24. The addition to... 

Barbarella and coworkers172 have studied the conformational properties of thiolane-1-oxide (187), its mono- and di-methyl derivatives (188-194) and trans-2-thiahydrindane-2-oxide (195) using force-field calculations and 1H, 13C and 17ONMR. They concluded that the overall conformational preference depends on the substituents and their locations... 

The molecular mechanics method314 has been applied to the calculation of conformational properties of the thiane, dithiane and trithiane oxide systems315, which are... 

The same inversion occurs in the case of the trans isomer10. Changes in conformational properties when passing from the neutral to the corresponding radical anion is a recent and well-documented topic in conformational analysis17-21. 

The ESR spectra of a large variety of sulfonyl radicals have been obtained photolytically in liquid phase over a wide range of temperature. Some selected data are summarized in Table 2. The magnitudes of hyperfine splittings and the observations of line broadening resulting from restricted rotation about the C—S bond have been used successfully in conjunction with INDO SCF MO calculations to elucidate both structure and conformational properties. Thus the spin distribution in these species is typical of (T-radicals with a pyramidal center at sulfur and in accord with the solid-state ESR data. 

When a Lewis acid coordinates to a base, the resulting complex can have conformational properties that influence reactivity. Coordination of SnCl4 with aldehydes and esters, for example, leads to a complex where the conformation is determined by interactions of the C=0"-SnCl4 unit with substituents attached to the carbonyl. 

The structures and conformational properties of a simple hemicarcerand, created earlier by Cram, see <96JA5590>, as well as the complexation and decomplexation with guest molecules have been computationally studied <96JA8056>. 

The majority of NNRTIs share common conformational properties and structural features that allow them to fit into an asymmetric, hydrophobic pocket about 10 A away from the catalytic site of the HlV-1 RT, where they act as non-competitive inhibitors (Kohlstaedt et al. 1992). However, the NNRTIs select for mutant virus strains with several degrees of dmg resistance. 

Our first exploration of property space was focused on acetylcholine. This molecule was chosen for its interesting structure, major biological role, and the abundant data available on its conformational properties [15]. The behavior of acetylcholine was analyzed by MD simulations in vacuum, in isotropic media (water and chloroform) [16] and in an anisotropic medium, i.e. a membrane model [17]. Hydrated n-octanol (Imol water/4mol octanol) was also used to represent a medium structurally intermediate between a membrane and the isotropic solvents [17]. 

Molecules of the simpUcity of ethane or the complexity of proteins and DNA adopt different conformations. In the case of ethane this gives rise to the notion of a staggered and eclipsed bond, whereas proteins form an array of complex structural elements and DNA - the famous double hehx. The understanding of the conformational properties of small molecules is an important factor in computational approaches contributing to drug discovery. 

T. Iwashita, Y. Mino, H. Naoki, Y. Suguira, and K. Nomoto, High-resolution proton nuclear magnetic resonance analysis of solution structures and conformational properties of muguneic acids and its metal complexes. Biochemistry 22 4842 (1983). 

Freire, /. /. Conformational Properties of Branched Polymers Theory and Simulations. VoL 143, pp. 35-112. 

Milas, M. and Rinaudo, M., Investigation on conformational properties of xanthan in aqueous solutions, in Solution Properties of Polysaccharides, Brant, D. A., Ed., ACS Symp. Ser., No. 150, American Chemical Society, Washington, D.C., 1981, 25-30. 

The conformational properties of various 1,1 -diheteroferrocenes (7-10) have been the subject of three computational studies using extended Huckel methods.19,46 471,1 -Diphosphaferrocene has also been studied using the Fenske-Hall approach.48 and an MS Xa method.46 Where they overlap, the four treatments are in reasonable qualitative agreement. 

---