Calculated Conformational Energies

We have searched the literature for publications comparing the performance of several different force fields in regard to their ability to reproduce experimental conformational energies. The results of this search are summarized in Table 1.14,15,17,19,24-27 

As Table 1 indicates, only a handful of such studies have been reported. In general, the developer of a force field validates the force field by testing and describing its ability to reproduce a selected set of experimental data, including conformational energies comparisons with other force fields, however, are scarce. Moreover, if such comparisons are made, the data set used often is limited, and the overlap of data between different validations is small. In the 

CHARMm 3.2 ChemSD Plus 3.1 Chem-X (Jan 89) CFF91/93 Cosmic CVFF 

In the study by Anet and Anet the abilities of nine different force fields were tested to reproduce geometry and energy data on a single molecule cis-sy -cis-perhydroanthracene. The aim of this study was to test the performance of force fields with experimental data not available at the time of force field parameterization. Experimental conformational energy data (inversion energy barrier) was best reproduced by the Boyd force field, followed by MM2 and the White-Bovill force field. Except for MM2, the force fields included in this study are not extensively used today. A discussion of these earlier force fields has been published.  

Clark et al.i compared the performance of the TRIPOS 5.2 force field to that of MM2 (version unspecified) for calculations of conformational and stereochemical energy differences. The stereochemical data set included cis versus trans energy differences for methyl-substituted or polycyclic hydrocarbon rings. Two sets of data including a total of 26 molecules and 29 experiments were used. The rms errors for MM2 were 0.5 and 0.8 kcal/mol for the conformational and stereochemical data set, respectively, whereas those of TRIPOS 5.2 were 0.8 and 1.7 kcal/mol. 

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I. Pettersson, T. Liljefors, Molecular mechanics calculated conformational energies of organic molecules a comparison of force fields, in Reviews in Computational Chemistry, Vbl. 9,... 

Fig. 8.3 Calculated conformational energy display values less than 2kcalmol ligands penalties of the protein-bound ligands 1-36. with five to eight rotors display values less The energy penalty increases with the number than 4kcalmol and ligands with eight to 11 of rotors. Ligands with one to four rotors rotors display values less than 6kcal mol. ...

Cornell, W. D. Cieplak, P. Bayly, C. I. Kollman, P. A., Application of RESP charges to calculate conformational energies, hydrogen bond energies, and free energies of solvation, J. Am. Chem. Soc. 1993,115, 9620-9631. 

Ingrid Pettersson and Tommy Liljefors, Molecular Mechanics Calculated Conformational Energies of Organic Molecules A Comparison of Force Fields. 

J. M. Wang, P. Cieplak, and P. A. Kollmann, How well does a restrained electrostatic potential (RESP) model perform in calculating conformational energies of organic and biological molecules J. Comput. Chem. 21, 1049 1074 (2000). 

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. 

Using Approximate Equilibrium Geometries to Calculate Conformational Energy Differences... 

Pettersson, 1. and Liljefors, T. 1996. Molecular Mechanics Calculated Conformational Energies of Organic Molecules A Comparison of Force Fields , in Reviews in Computational Chemistry, Vol. 9, Lipkowitz, K. B. and Boyd, D. B., Eds., VCH New York, 167. 

Techniques used to calculate conformational energies are NR for "no relaxation", PR for "partialrelaxation", and FR for "fullrelaxation". 

Conformational energies are calculated for chain segments in poly(vlnyl bromide) (PVB) homopolymer and the copolymers of vinyl bromide (VBS and ethylene (E), PEVB. Semlempirical potential functions are used to account for the nonbonded van der Waals and electrostatic Interactions. RIS models are developed for PVB and PEVB from the calculated conformational energies. Dimensions and dipole moments are calculated for PVB and PEVB using their RIS models, where the effects of stereosequence and comonomer sequence are explicitly considered. It is concluded from the calculated dimensions and dipole moments that the dipole moments are most sensitive to the microstructure of PVB homopolymers and PEVB copolymers and may provide an experimental means for their structural characterization. 

The possible backbone phosphodiester conformations in a dinucleotide monophosphate and a dinucleotide triphosphate are investigated by semiempirical energy calculations. Conformational energies are computed as a function of the rotations o and <0 about the internucleotide P-0(3 ) and P-015 1 linkages, with the nucleotide residues themselves assumed to be in one of the preferred [C(3 )-e/K/o) conformations. 

Pettersson I, Liljefors T. Molecular mechanics calculated conformational energies of organic molecules a comparison of force fields. In Lipkowitz KB, Boyd DB, eds. Reviews in Computational Chemistry. Vol. 9. New York VCH, 1996 167-189. Liljefors T, Gundertofte K, Norrby PO, Pettersson I. Molecular mechanics and comparsion of force fields. In Bultinck P, Winter HD, Langenaeker W, Tollenaere JP, eds. Computational Medicinal Chemistry for Drug Discovery. New York Marcel Dekker, 2004 1-28. 

Flexible molecules with single bonds can readily interconvert into different conformers, provided there is sufficient energy. It is possible to calculate conformational energies and thus predict preferred conformations b ... 

As a corollary to the foregoing discussion, the computations also provide an answer to the controversial question of the influence of assumed geometry on the calculated, conformational-energy differences. The results present evidence ofthe necessity of at least a partial optimization, including the main bond lengths and bond angles, in the theoretical calculations of molecules exhibiting the anomeric and exo-anomeric effects. - ... 

Figure 6 Calculated conformational energy differences (axial-equatorial) in kcal/mol for N-methylpiperidine. The dashed line shows the experimental value.

Table 1.5. Corey s A, G and U Values for Calculating Conformational Energies of Cyclohexane Derivatives...

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