False energy minima

Figure 1. Potential energy values as some (unspecified) conformational variable is changed. A represents a local (false) minimum and C represents the global minimum (assuming that all other variable parameters are also in the least energetic conformations).

As in the case of minimum detectable activity (Sec. 2.20), two types of errors are encountered when one tries to identify peaks in a complex energy spectrum. Type I arises when background fluctuations are falsely identified as true peaks. Type II arises when fluctuations in the background obscure true peaks. Criteria are set in the form of confidence limits (see Sec. 2.20 and Ref. 38) that can be used to avoid both types of errors. 

The first type of program, based on an unconstrained force field approach is more comprehensive but suffers from the limitation of the size of molecules that can be investigated due to the extent of computations needed. It is thus very apt for the study of smaller molecules or systems of molecules up to 40-60 atoms, but this limitation is also fictitious because it really depends on the capacity and calculation rate of the computer used. Such unconstrained force field programs tend to suffer furthermore from the problem that the automatic search for the minimum of energy might lead the program to minimize on a local rather than total minimum, and if particular attention is not exercised completely false results can be obtained (the black-box syndrome). 

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