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energy minimization. The minimization step removes most steric strains, but falls short
of the full dynamical equilibration that might better predict the structural rearrangements
involved with domain motion; further it assumes the trajectory of motion is linear.
FRODA can find nonlinear trajectories connecting two structures but enforces only steric,
covalent, and hydrogen-bonding constraints on a geometric level without computing
energetic interactions. Morphing by using the Conformation Explorer would generate
equilibrated structures that represent more thermodynamically plausible trajectories of
motion. Morph-like movies can be generated which resemble available morph
trajectories but which were predicted based on a single structure rather than two.
A third possible application of the method is the exploration of possible alternate
conformations to elucidate function. One could potentially generate conformations that
position the protein’s active, binding, and functional sites where they would be needed to
perform a specific function. If the new configuration can be shown to be sterically
permitted and sufficiently stable, the geometric information obtained can help in the
design of experiments that would confirm or refute the proposed mechanism. For
example, one could use such coordinate sets to determine the optimal location of FRET
pairs. In one comparable experiment the structure of syntaxin 1 in complex with munc-
18 was known, but its conformation and dynamics as a monomer were unknown. The
known crystallographic coordinates were used to select logical location of FRET donor
and acceptor dyes, leading to an understanding of the conformational changes occurring
in the monomer. It was confirmed that one of the possible conformations of the
monomer was similar to that observed in the complex.[94] With an equilibrated
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