Searching of conformational space

A similar algorithm has been used to sample the equilibrium distribution [p,(r )] in the conformational optimization of a tetrapeptide[5] and atomic clusters at low temperature.[6] It was found that when g > 1 the search of conformational space was greatly enhanced over standard Metropolis Monte Carlo methods. In this form, the velocity distribution can be thought to be Maxwellian. 

High temperature searches of conformational space (see Quenched Dynamics" on page 78), can produce unwanted conformational changes, such as cis-tmnx peptide flips, ring inversions, and other changes that you cannot reverse easily by geometry optimization. You can use restraints to prevent these changes. 

Goodman J M and W C Still 1991. An Unbounded Systematic Search of Conformational Space. Journaloj Computational Chemistry 12 1110-1117. 

Finally, with all the current activity on the multiple-minima problem, which is essentially solved for oligopeptides and regular-repeating structures of fibrous proteins, we may hope to see further progress in treating larger molecules, that is, globular proteins, by more efficient searches of conformational space. 

Goodman, J. and Still, W.C. (1991) An unbounded systematic search of conformational space./. Comp. Chem. 12, 1110-1117. 

If nothing is known about the tertiary structure of the protein of interest, can anything be done to develop a reasonable model As mentioned earlier, complete searching of conformational space is impossible for proteins and other large molecules. However, several groups have developed methods to simplify the problem into one that is solvable. 

Fig. 16 Evolution of the free energy (BP86 with different protocols, kcal/mol) of conformers 9 and 5 of the Ph-I oxidative addition transition state as a function of adopted methodology. Conformer 9 shows the symmetrical Xantphos ligand that is typical of crystallographic studies conformer 5 is derived from an MD/MM search of conformational space. Atoms in gold highlight the phenyl ring of the Phi substrate, and H atoms have been omitted for clarity. See Fig. 15 for definition of BSl and BS2...

The method described above for the searching of conformational space has been applied [52] to a wide range of guest molecules in calixarenes. 

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