Conformational energetics

To evaluate the total free energy change, AG for the formation of a native structure form the random polypeptide chain, i.e. AG = -RT InK = AH - TAS for the process  

Random polypeptide chain Native protein The free energy change of the contributing forces/bondings can be expressed by  

int Free energy changes for short range interactions, i.e. hydrogen bonding, 

TABLE 5.13 Estimated contribution of individual factors to stability of a bypothetical protein of 100 residues at 25°C 

Note N for native state and D for denatured state, taken from Creighton (1983). 

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Step 1 of the parametrization process is the selection of the appropriate model compounds. In the case of small molecules, such as compounds of pharmaceutical interest, the model compound may be the desired molecule itself. In other cases it is desirable to select several small model compounds that can then be connected to create the final, desired molecule. Model compounds should be selected for which adequate experimental data exist, as listed in Table 1. Since in almost all cases QM data can be substimted when experimental data are absent (see comments on the use of QM data, above), the model compounds should be of a size that is accessible to QM calculations using a level of theory no lower than HE/6-31G. This ensures that geometries, vibrational spectra, conformational energetics, and model compound-water interaction energies can all be performed at a level of theory such that the data obtained are of high enough quality to accurately replace and... 

The second generation force fields for nucleic acids were designed to be used with an explicit solvent representation along with inclusion of the appropriate ions [28,29]. In addition, efforts were made to improve the representation of the conformational energetics of selected model compounds. Eor example, the availability of high level ab initio calculations on the conformational energetics of the model compound dimethylphosphate yielded... 

With respect to the carrier mechanism, the phenomenology of the carrier transport of ions is discussed in terms of the criteria and kinetic scheme for the carrier mechanism the molecular structure of the Valinomycin-potassium ion complex is considered in terms of the polar core wherein the ion resides and comparison is made to the Enniatin B complexation of ions it is seen again that anion vs cation selectivity is the result of chemical structure and conformation lipid proximity and polar component of the polar core are discussed relative to monovalent vs multivalent cation selectivity and the dramatic monovalent cation selectivity of Valinomycin is demonstrated to be the result of the conformational energetics of forming polar cores of sizes suitable for different sized monovalent cations. 

Such conformational dependence presents challenges and an opportunity. The challenges he in properly accounting for its consequences. In many cases, exact conformational energetics and populations in a sample may be unknown, and the nature of the sample inlet may sometimes also mean that a Boltzmann distribution cannot be assumed. Introducing this uncertainty into the data modeling process produces some corresponding uncertainty in the theoretical interpretation of data... 

Jorgensen, W. L., Maxwell, D. S., Tirado-Rives, J. Development and testing of the OPLS all-atom force field on conformational energetics and properties of organic liquids. J. Am. Chem. Soc. 

Development and Testing of the OPLS All-Atom Force Field on Conformational Energetics and Properties of Organic Liquids. 

N. Foloppe et al., Intrinsic conformational energetics associated with the glycosyl torsion in DNA A quantum mechanical study. Biophys. J. 82, 1554-1569 (2002)... 

Using what you know about the conformational energetics of substituted cyclohexanes, predict which of the two decalin isomers is more stable. Explain your reasoning. 

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