bond angles (allowing the bond dihedrals to vary). Such a model is adequate to describe a wide range of interesting organic molecules including proteins and drug-like ligands. We assume that the rigidity of the fragments is imposed only by intra-fragment energy. If other terms (e.g., an improper torsion term involving atoms from two fragments) contribute to the rigidity of a fragment, then we shall treat such terms as additional inter-fragment energies.

We apply the generalized MTS method to this system with $m=3$, the intra-fragment energy given by $E_1$, the inter-fragment bond constraints given by $E_2$, and with $E_3$ accounting for all the other energies. The argument given above allows us to pass to the limit of strictly rigid fragments. The method is then equivalent to a standard MTS method where the “elementary” moves consist of rigid displacements of each fragment which are Boltzmann accepted with energy $E_\mathrm h =
E_2$. A sequence of $n = n_2$ such moves are made with the result Boltzmann accepted with energy $E_\mathrm s = E_3$. A possible prescription [@karney05b §VII] for the rigid displacements of the fragments is to translate the fragment by a vector sampled from an isotropic 3-dimensional Gaussian and to rotate 