Random search mechanism

The renaturation process of globular proteins takes place within 10 and 10" seconds. Internal molecular rotations are known to be in the order of 10 seconds Taking into account only three energetically favorable conformational states for each amino acid, a relatively small protein of 150 residues can potentially adopt more than 10 conformations. A comparison of these figures illustrates in an impressive manner that the time available to a protein for the folding process is by far not sufficient to find the energetically most favorable conformation by a random search mechanism. 

The connection (arrow) between stimulus and attached key allows the scanner to go directly from the found target stimulus to the target key without any new search. This saves 1 cycle per trial in v22. If the arrow alone is capable of activating the target key, the random search mechanism is not necessary. 

The exact nature of this problem has been rethought, and a random search is now not considered to be a good description of folding. Harrison and Durbin suggested that there are many ways of reaching the native state in reasonable time, so that a specific pathway (from unfolded to folded state) does not have to be postulated. Recently, this kind of model has been further developed using lattice modelling studies and statistical mechanical models. 

A program system called SIDYS using simulation techniques and parameter identification was applied to the absorption data. It includes random search techniques, Rosenbrock strategy, quasi-Newton methods, and lattice search. It runs on a mainframe computer and provides good agreement between simulated and experimental data. On the other hand, it proves that the data of this type of mechanism are not well conditioned and the quality of the evaluation drastically depends on the parameter set chosen [155]. 

Inherent to the molecular mechanics method is a set of analytical expressions for the total energy of a system. It is a simple matter to derive the first and second derivatives of the energy expression. The first derivatives define the forces on the molecule. At a minimum there are no forces—the system is "at rest". Thus, geometry optimization involves minimizing the first derivatives—a process that can be much more efficient than just randomly searching for a minimum. Furthermore, at a minimum, all second derivatives are positive. 

Although it has not been demonstrated, it seems plausible that both models are operating. At each stage of the process, substructiu es may be formed by a diffusion-collision mechanism. At each level of organization and in in different parts of the molecule, a random search can conceivably lead to the formation of either right or wrong structures these last ones have to be corrected to achieve the right structure of the whole molecule. 

Ferguson D M and D J Raber 1989. A New Approach to Probing Conformational Space with Molecular Mechanics Random Incremental Pulse Search, journal of the American Chemical Society 111 4371-4378. 

Ferguson, D. M. and Raber, D. J. (1989) A new approach to probing conformational space with molecular mechanics random incremental pulse search. J. Am. 

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