Protein structure energetics

CA Schiffer, JW Caldwell, PA Kollman, RM Stroud. Prediction of homologous protein structures based on conformational searches and energetics. Pi otems 8 30-43, 1990. 

To conclude, although the models used in lattice simulations are very simplified, the results provide general information on possible protein folding scenarios, albeit not on the detailed behavior of specific proteins, which would require more complex models and more accurate potentials. The contribution made by these simulations is that they enable an analysis of the structures, energetics, and dynamics of folding reactions at a level of detail not accessible to experiment. 

Certain side-chain conformations are energetically mote favorable than others. Computer programs used to model protein structures contain rotamer libraries of such favored conformations. 

Reva, B. and S. Topiol. 2000. Recognition of protein structure determining the relative energetic contributions of fS-strands, a-helices and loops. Pac Symp Bio-comput 5 165-175. 

Thus the energetics of a protein are intimately connected with structure and structural mobility. It is therefore important to investigate these structural features. In the following section we consider the type of structural information that different techniques can provide. Then general conclusions from these techniques are used to discuss the nature of protein structure as it is now understood. Finally, the structure energetics and functions of a few specific proteins are briefly discussed. 

Other spectroscopic methods cannot provide the same overall picture of protein structure or dynamics. However, they can give information about specific atoms or groups in the protein. In order to gain detailed information from these techniques, it is generally necessary to study metal atoms, which in some cases are a natural part of the protein and in other cases may be specifically introduced. Techniques such as UV, visible, Raman, and epr spectroscopies provide information about the metal atom and its environment, which is concerned both with structural features and with energetic features. 

Computer simulations are regularly performed of the energetics of protein structure and their interactions with ligands using potential energy functions for the forces described so far. The energy functions are of necessity simplifications, but they are calibrated on experimental data. A minimalist model uses equation 11.3.15... 

Owing to the complexity of protein structures, model compounds have often been employed in estimating thermodynamic parameters for protein unfolding. The utility of these parameters depends on the validity of the choice of a model system, i.e., how well the model system mimics the process of transferring different functional groups from the protein interior into the solvent. In principle, one would like to choose a reference state that is similar energetically to the protein interior. 

Atomic contacts that are not abundant in the protein structure database are good indicators of local model-building problems [63]. Atomic contacts are observed because they are energetically favored. Real structures cannot tolerate too many unfavorable interactions. Unis fora model to be correct, only a few infrequently observed atomic contacts are allowed. This quality control of local packing has proven to be the most powerful tool for the detection of abnormal structures. 

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