Structure search Procedure

Chemical reactions provide another level of chemical structure searching. In this case the idea is to search for preparations of compounds, reactions of substances, or the molecular transformation from substance A to substance B. While the first two cases can be handled by the normal structure search procedures, the third case requires an extension of this algorithm. It is also possible to perform searches of functional group transformations. However, it must be kept in mind that such searches require a certain time to complete. If the query structures are very general, the number of structures to be compared is very high and the atom-by-atom match may take a long time to complete (see Reaction Databases). 

HyperChem offers a Reaction Map facility under the Setup menu. This is needed for the synchronous transit method to match reactants and products, and depending on X (a parameter having values between 0 and 1, determining how far away from reactants structures a transition structure can be expected) will connect atoms in reactants and products and give an estimated or expected transition structure. This procedure can also be used if the eigenvector following method is later chosen for a transition state search method, i.e., if you just want to get an estimate of the transition state geometry. 

It is important to note that the applied rules are not the pure retrosynthetic rules. The described structure dissection procedure also takes into account the structures of typical privileged motifs and is directed to the search of structural chemotypes with selective action against particular receptors. 

Grosse-Kunstleve, R. W. and Adams, P. D. (2003). Substructure search procedures for macromolecular structures. Acta Crystallogr. D 59,1966-1973. 

At the very bottom level of most structure handling algorithms two structures are compared atom by atom and bond by bond (ref. 1). However, the preprocessing steps, the I/O conditions, the constraints in the query or in the reference structures, and requirements for a match or failure differ considerably from application to application. The most frequent used structure manipulating procedures are substructure and superstructure searches. 

In the case of non-equilibrium conditions, the crossing point is located for a frozen solvent structure. During an electron transition the Franck-Condon principle is applicable and the solvent nuclei remain fixed during the transition. Consequently, the solvent structure is in equilibrium with the charge distribution of the solute in its ground state. The crossing point search procedure is performed in presence of this solvent structure. 

M. H. Lambert and H. A. Scheraga, J. Comput. Chem., 10,798 (1989). Pattern Recognition in the Prediction of Protein Structure. II. Chain Conformation from a Probability-Directed Search Procedure. 

In addition to structure determination from powder diffraction data as described earlier, another area of considerable current interest is the computational prediction of crystal structures based on energy simulation techniques. In such work, the potential energy, E(r), is computed as a function of the set of variables T that define the structure (the unit cell and space group are usually also included as variables in such calculations), and the E r) hypersurface is searched to find the structure of minimum energy. Representative examples of work in this field may be found in Refs. [74-79], and some work involving the use of evolutionary algorithms to carry out the search procedure has been reported [80-82]. 

Desmet et al. (291) used a truncated (deadend elimination) search procedure to bind flexible peptides to the MHC I receptor. The translation/rotational space covered 6636 relative orientations and each nonglycine/proline residue of the peptide had 47 main-chain con-formers. Side chains had threefold rotations about their chi angles and 28 side chains of the receptor were allowed to rotate. Seventy-four low energy structures were obtained with an average rmsd of 1 A. The lowest energy structure had an rmsd of 0.56 A. Peptides up to 20 residues were docked with this procedure. 

---