The prediction of the three-dimensional structures of the native states
of proteins from the sequences of their amino acids is one of the most
important challenges in molecular biology. An essen tial task for
solving this problem within coarse-grained models is the deduction of
effective interaction potentials between the amino acids. Over the
years, several techniques have been developed to extract potentials that
are able to discriminate satisfactorily between the native and nonnative
folds of a preassigned protein sequence. In general, when these
potentials are used in actual dynamical folding simulations, they lead
to a drift of the native structure outside the quasinative basin. In
this article, we present and validate an approach to overcome this
difficulty. By exploiting several numerical and analytical tools, we set
up a rigorous iterative scheme to extract potentials satisfying a
prerequisite of any viable potential: the stabilization of proteins
within their native basin (less than 3-4 Angstrom RMSD). The scheme is
flexible and is demonstrated to be applicable to a variety of
parameterizations of the energy function, and it provides in each case
the optimal potentials.
