How Is Molecular Flexibility Handled

When molecules are built up atom by atom, all conformations of the 

Use of multiple conformations is the most straightforward way of dealing with fragment flexibility. The GROW program of Moon and Howe 

The problem with defining conformations for each fragment is that subsequently, during the building procedure, the different conformations are treated as separate fragments, so the combinatorial problem becomes too large 

Leach and Kilvington have used the original random tweak method to join already placed fragments with simple hydrocarbon chains. This application, which is more restricted than that described above, allows the placement and fitting of general fragments and their associated interaction sites. 

---