  Recent single-molecule force measurements on single-domain proteins have
highlighted a three-state folding mechanism where a stabilized intermediate
state (I) is observed on the folding trajectory between the stretched state and
the native state. Here we investigate on-lattice protein-like heteropolymer
models that lead to a three-state mechanism and show that force experiments can
be useful to determine the structure of I. We have mostly found that I is
composed of a core stabilized by a high number of native contacts, plus an
unstructured extended chain. The lifetime of I is shown to be sensitive to
modifications of the protein that spoil the core. We then propose three types
of modifications--point mutations, cuts, and circular permutations--aiming at:
(1) confirming the presence of the core and (2) determining its location,
within one amino acid accuracy, along the polypeptide chain. We also propose
force jump protocols aiming to probe the on/off-pathway nature of I.
