Conformational Sampling and the Global Minimum Problem

The methods described in Section 12.2 can only locate the nearest minimum, which is normally a local minimum, when starting from a given set of variables. In some cases, the interest is in the lowest of all such minima, the global minimum in other cases it is important to sample a large (preferably representative) set of local minima. Considering that the number of minima typically grows exponentially with the number of variables, the global optimization problem is an extremely difficult task for a multidimensional function. It is often referred to as the multiple minima or combinatorial explosion problem in the Uterature. 

First angle Second angle Third angle 

The systematic, or grid, search is only possible for small molecules. For larger systems, there are methods that can be used for perturbing a geometry from one local minimum to another. Some commonly used methods for conformational sampling are  

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