Abstract
The extended simulated annealing process (ESAP) is a useful method
for modeling the partial structure of proteins [J. Higo et al., Biopolymers,
32, 33 (1992)]. In ESAP, a protein molecule is divided into two parts:
small, flexible fragments constituting the concerned partial structure,
and the remaining part, for which the structure is kept rigid during the
simulation. We have improved the program of ESAP so that it can be adapted
to general macromolecules. Any sidechain on the rigid part can be set to
r otate. Soft repulsion between van der Waals spheres is introduced to
avoid conformational trapping into local minima. This improved program
was tested for modeling structural changes caused by eight kinds of amino
acid mutation at the 86th residue in T4 lysozyme. For each mutant we obtained
a model structure that was close to the X-ray structure. The root mean
square (rms) deviations from the X-ray structure were 0.3 to 0.8 ? for
all heavy atoms and about 0.2 ? for the main-chain atoms. We also modeled
the structure of an Ile mutant, for which the X-ray structure has not yet
been reported. ESAP can be used to model structural changes due to a single
residue mutation in proteins.