  In molecular mechanics, current generation potential energy functions provide
a reasonably good compromise between accuracy and effectiveness. This paper
firstly reviewed several most commonly used classical potential energy
functions and their optimization methods used for energy minimization. To
minimize a potential energy function, about 95\% efforts are spent on the
Lennard-Jones potential of van der Waals interactions; we also give a detailed
review on some effective computational optimization methods in the Cambridge
Cluster Database to solve the problem of Lennard-Jones clusters. From the
reviews, we found the hybrid idea of optimization methods is effective,
necessary and efficient for solving the potential energy minimization problem
and the Lennard-Jones clusters problem. An application to prion protein
structures is then done by the hybrid idea. We focus on the $\beta$2-$\alpha$2
loop of prion protein structures, and we found (i) the species that has the
clearly and highly ordered $\beta$2-$\alpha$2 loop usually owns a
3$_{10}$-helix in this loop, (ii) a "$\pi$-circle"
Y128--F175--Y218--Y163--F175--Y169--R164--Y128(--Y162) is around the
$\beta$2-$\alpha$2 loop.
