Protein representations

To overcome the limitations of the database search methods, conformational search methods were developed [95,96,109]. There are many such methods, exploiting different protein representations, objective function tenns, and optimization or enumeration algorithms. The search algorithms include the minimum perturbation method [97], molecular dynamics simulations [92,110,111], genetic algorithms [112], Monte Carlo and simulated annealing [113,114], multiple copy simultaneous search [115-117], self-consistent field optimization [118], and an enumeration based on the graph theory [119]. 

Although the folding of short proteins has been simulated at the atomic level of detail [159,160], a simplified protein representation is often applied. Simplifications include using one or a few interaction centers per residue [161] as well as a lattice representation of a protein [162]. Some methods are hierarchical in that they begin with a simplified lattice representation and end up with an atomistic detailed molecular dynamics simulation [163]. 

Richardson JS, Richardson DC, Tweedy NB, Gemert KM, Quinn TP, Hecht MH, Erickson BW, Yan Y, McClain RD, Donlan ME. Looking at proteins representations, folding, packing, and design. Biophys J 1992 63 1185-1209. 

Figure 3 The Escherichia coli pyrophosphatase hexamer in a standard protein representation the spirals are a-helices and the arrows are /3-strands. The unit cell axes are marked with orange lines and each monomer has a different color (a) viewed along one of the twofold axes. The twofold rotation axis, marked with an ellipse, relates the orange and red monomers, and the yellow and purple monomers (and the hard-to-see cyan and blue monomers) to each other, (b) A view along the threefold axis, marked with a triangle. The threefold axis relates the orange, purple, and cyan monomers to each other, as well as the yellow, red, and blue ones to each other.

Figure 2 The simplified protein representation used in the QPACK model evaluation procedure for the sequence Leu-Tyr-Trp-Lys. The all-atom polypeptide structure is depicted by thin lines. The simplified model is shown with thick lines. Aliphatic residues are represented by pseudoatoms at their side chain centers of mass. Aromatic residues have additional pseudoatoms placed at their ring centroids.

II. Protein Representation Force Field, and Sampling Protocols... 

PROTEIN REPRESENTATION, FORCE FIELD, AND SAMPLING PROTOCOLS... 

The accuracy of a reduced protein representation could be improved by taking into account some internal degrees of freedom of the side chains... 

A similar methodology, but one based on a completely different protein representation [139,140] (that are discussed in Sections V and VI), was employed by Kolinski and co-workers with a similar fraction of correctly predicted stmctures [133]. An important advantage of this method was its computational speed and nicer scaling of computational cost against protein chain length. Thus, the prediction of stmctures of larger proteins via ab initio folding became possible. 

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