Conformations structure prediction models

Unlike linear B-cell epitopes, conformational epitope prediction models were limited by the need to understand antigen-antibody (Ag-Ab) complex structures before applying these algorithms. As with the linear epitopes, researchers started by seeking structural... 

In protein structure prediction, potentials are used to assign an energy-like quantity to a conformation of a protein molecule. If this quantity enables us to distinguish the native state of a protein, the potential is regarded as a reasonable model for a protein-solvent system. The rationale behind this relies on two assumptions (a) a solved protein in its native state can be described by an ensemble of closely related conformations, and (b) in this state the system is in the global minimum of free energy. Virtually all techniques designed for structure prediction are based on these principles [3,4]. 

The results of the first four polymers are listed in Table I the internal rotation angles of the main chain, x. and x , the number of monomeric units per turn, N, for the calculated stable conformations, and also the values for the structure determined by x-ray analyses. In the case of polypropylene, the number of monomeric units per turn is 2.91, very close to the x-ray value of 3.0. This result for polypropylene is essentially the same as those of Natta et al. (32) and Liquori et al. (33). For the three other polymers, good agreements were also obtained between the predicted models and x-ray structures in spite of the simple assumption of considering only intramolecular interactions. This... 

Method for Protein Modeling and Design Applications to Docking and Structure Prediction from the Distorted Native Conformation. 

In lattice models, the location of each element on the lattice can be stored as a vector of coordinates [(X, F,), (X2, Y2), (X3, Y3),..., (Xn, F )], where (X Y,) are the coordinates of element i on a two-dimensional lattice (a three-dimensional lattice will require three coordinates for each element). Since lattices enforce a fixed geometry on the conformations they contain, conformations can be encoded more efficiently by direction vectors leading from one atom (or element) to the next. For example in a two-dimensional square lattice, where every point has four neighbors, a conformation can be encoded simply by a set of numbers (Lu L2, L3,..., L ), where L, g 1, 2,3,4 represents movement to the next point by going up, down, left, or right. Most applications of GAs to protein structure prediction utilize one of these representations. 

Fig. 11. Gating as a consequence of the structural interplay between two gates . (A) The present data are interpreted according to a minimal four-state sequential model in which movement of the channel intracellular gates (TM2) allows the selectivity filter to fluctuate and enter a conductive conformation that corresponds to the open state. In transit from the closed state the channel must populate an intermediate open, non-conductive state. As these states are conformationally coupled, the model predicts that the intracellular gate is unlikely to close before the selectivity filter returns to its non-conductive state. (B). The model suggests that the duration of a burst is governed by the C Cg equilibrium, occurring in the intracellular gate, while the intraburst activity (channel flicker) is determined by the Cg O transition.

We had hoped that the semi-empirical calculations would maintain the conformer energies in the order predicted by MM2. Unfortunately this was not the case, although the energy differences were often smaller than those computed by MM2, especially for the smaller cage structures. In addition, the structure predicted to be the lowest-energy conformer by MM2 did not always maintain that status after semi-empirical optimization. Furthermore, the lowest energy structures computed by the three semi-empirical models did not always come from the same MM2 starting structure. In short, there was very little coherence between the MM2 and semi-empirical results. 

The alternating access transport model has been used to describe the mechanism by which substrates are transported across the membrane via the monoamine transporters (Forrest et al., 2008). This model postulates that the transporter can exist in at least two conformations. These conformations include an extracellularly facing form that is open to the extracellular environment and can bind substrate and Na" and CF ions (Forrest et al., 2008). An intracellularly facing form allows the release of substrate into the cell and the binding of the countertransported ion to reverse the conformation of the transporter (Forrest et al., 2008). The alternating access model is supported by recent crystal structures of other transporters (Weyand et al., 2008 Faham et al., 2008). Two additional conformations of these transporters have also been described. A closed-closed conformation is predicted that prevents accessibility of substrate and ions from either side of the transporter. This closed-closed conformation was observed in the crystal structure of a leucine transporter... 

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