Structure grid search

Conformational isomers represent minima on an energy surface, and all structures and the corresponding strain energies can be obtained by a careful analysis. This can be performed manually (such as in Sections 17.3 and 17.4) or automatically. An automatic procedure may involve a systematic search (grid search methods), a stochastic search (e.g., torsional Monte Carlo or cartesian stochastic, i.e., the random kick method) or molecular dynamics (see Chapter 5 and Section 16.5). Implemented in MOMEC is a random kick stochastic search module, and this has been shown to lead to excellent results, not only for conformational equilibria, but also for distributions of configurational isomers[37]. 

Considering only the conformations with a total energy less than 10 kJ mol" above the lowest energy conformations, the same ensemble of conformations as detected in the structural database searches was found. With this systematic backbone and side chain rotamer search approach, we analysed only 144 structures instead of the 10 structures for a conventional grid search with 36° intervals for 6 dihedral angles. 

In grid searching (GS), each torsion angle is examined, but the. structure is not subjected to geometry optimization. 

To approximately locate the global minimum i.e., to obtain a good quality crystal structure solution) in a reasonable amount of time, grid search methods should be replaced by the stochastic ones, based on a random sampling of the parameter space. This technique, called Monte Carlo MC), has been widely used in other scientific fields to simulate the behavior of complex systems. Its application to crystal structure determination from powder diffraction data has been developed by many authors the main strategies are outlined below. 

Among the currently available methods we quote ZIP-PROMET, which can only handle rigid models and generates the trial structures by a stepwise construction of dimers and layers, UPACK which uses a grid search algorithm, and Polymorph Predictor, which uses a SA search. 

---