Contact Potential for Global Identification of Correct Protein Folding
The classical protein folding problem is to predict the three-dimensional (3D) conformation of a protein given only its amino acid sequence. In the thermodynamic approach one attempts to simulate this by choosing some kind of potential function of conformation and then searching for the conformation(s) having the global minimum of this function. There are two interrelated problems that need to be solved in order to ensure the calculations are feasible and to get correct answers: How to represent conformations, and how to construct the function? The standard approach to computational conformational analysis, molecular mechanics, represents each atom in the molecule as a point in 3D space, so that atoms can move in a continuous fashion by smoothly changing their x, y, and z coordinates. Sometimes the atomic Cartesian coordinates are calculated from specified internal coordinates (bond lengths, bond angles, and torsion angles), but in any case conformational movements are smooth and continuous. Potential functions of conformation are generally chosen as long sums of two-, three-, and four-atom interactions, where each term is a continuous function of atomic coordinates, often having some physical significance. The adjustable parameters within these terms are subsequently varied so as to reproduce some selection of experimentally observed conformations, crystal structures, known bond-rotation barriers, enthalpies of sublimation, vibrational frequencies, etc.
KeywordsNative Conformation Reference Structure Contact Potential Contact Function Residue Type
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