A COMBINED MODEL-BUILDING AND DISTANCE GEOMETRY APPROACH TO AUTOMATED CONFORMATIONAL-ANALYSIS AND SEARCH

A combined template-joining/distance geometry approach to automated conformational analysis and search is described. The method is based on a previously reported heuristic, knowledge-based system in which conformations of a molecule are constructed by joining together prestored fragments called conformational units. The program identifies the conformational units to be used in a given molecule from among those contained in a knowledge base. A difficulty with such an approach is that the knowledge base may not contain all the units needed to analyze a particular molecule. Thus in the combined algorithm, distance geometry is used to search the conformational space of those fragments that the system does not 'know' about. By this means the system is able to automatically aquire conformational knowledge. We also describe how the combined approach can be used to construct conformations of highly strained ring systems which can be problematic for template-joining algorithms.