Conformations energy calculations

M Vasquez, G Nemethy, ElA Scheraga. Conformational energy calculations on polypeptides and proteins. Chem Rev 94 2183-2239, 1994. 

Fig. 20. A. Conformation of the Valinomycin-cation complex derived for solution using a combination of proton magnetic resonance data and conformational energy calculations. This structure agrees within tenths of an Angstrom with the crystal structure subsequently determined (100) and shown in Fig. 21. Reproduced with permission from Ref.99).

Fig. 21. Crystal structure of the Valinomycin-K+ complex. Reproduced with permission from Ref.100). This crystal structure confirmed within tenths of an Angstrom the structure derived previously in solution 97 98) and by means of conformational energy calculations...

This last section presents some practical applications of conformational analysis in drug discovery projects. To illustrate the importance of conformational energy calculations we draw mainly on examples taken from our experience and chosen to reflect different scales of problems that can be addressed. 

Gundertofte, K., Liljefors, T., Norrby, P.-O., Pettersson, I. A comparison of conformational energies calculated by several molecular mechanics methods. 

According to conformational energy calculations, the POx chain can assume conformations other than planar zigzag, such as T3G and T2G2, and, according X-ray and IR studies, these two conformations are stable. The POx assuming them is thicker than the planar zigzag one, so that it may be included in / -CD as well as a-CD. 

Conformational Energy Calculations in Isotactic and Syndiotactic Polymers... 

Weintraub, H. J. R., and Nichols, D. E. (1978) Conformational energy calculations of some amphetamine analogs using a new solvation model. Int. J. Quant. Chem., QBS 5 321-343. 

The molecular mechanics technique has been called by many different names, including Westheimer method, strain-energy method, conformational energy calculations, empirical potential energy calculations, atom-atom pair potential method, and force field calculations. Empirical force field is widely used, but somewhat long, and many authors omit empirical, leading to confusion with spectroscopic force field calculations. Molecular mechanics (11) now appears to be favored (10a) and is used (abbreviated as MM) throu out this chapter. 

Transitions such as this in monomer ring geometries, which can arise spontaneously in MD simulations but which cannot be easily incorporated into static conformational energy calculations, could have important consequences if they occurred in polysaccharides. 

Figure 3. The initial exocyclic C-0 retainers used for conformational energy calculations on the deoxytetro-furanoses 7 (A), 8 (B), 9 (C) and 10 (D). The Cl-01 rotamers were chosen to optimize the "exoanomeric...

The internal flexibility of oligosaccharides is a major obstacle to interpretation of experimental data. To deduce three-dimensional structure, one must, therefore, be able to correctly model internal flexibility. Various methods and results for conformational energy calculations for oligosaccharides have recently been reviewed (9-13). Therefore, no attempt will be made here to describe such efforts to calculate conformational energy surfaces. 

The role of nonstaggered conformations in PE and PP is discussed in some detail. In incorporating such conformations into RIS treatments, it is essential to choose rotational states as to assure equitable sampling of configuration space. Tacit identification of rotational states with minima in the conformation energy surface, a common practice, may lead to serious errors. The significance and limitations of conformational energy calculations are discussed. 

The given model uses results of conformational energy calculations by Damewood, Jr., J. R. West, R. Macromolecules 1985, 18, 159. 

Conformational energy calculations are carried out on 2,4,6-trimethylheptane as a model for PP using energy minimization with all internal degrees of freedom allowed to participate. Caicd. quantities 0/r)/2 d (In 0 I d T [for values of pr = 1 (perfectly isotactic) to pr = 0 (perfectly syndiotactic)]... 

The epimerization equilibria for the diastereomers of 2,4,6,8-tetramethylnonane and 2,4,6,8,10-pentamethylundecane are determined and the results are interpreted in terms of a RIS model. The results yield correct values for the optical activity and are consistent with conformational energies calculated from experimental values of the unperturbed dimensions of PP. 

Conformational energy calculations are coupled with dipole moment measurements to derive a conformational description of P2VP. When an RIS model is used to calculate the dipole moments of P2VP chains with different stereosequences, it is found that the calculated dipole moments are nearly independent of the P2VP stereosequence. 

Conformational energy calculations indicate the g state to be at least 30 kJ mol-1 higher than the t and the g states. With the exclusion of the former conformation, all interactions of long range are eliminated, and the statistical weight matrices for the respective bond pairs reduce to 2x2 order. 

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