l - People

aborted. This marked the corresponding cell as being on the boundary of the accessible
phase space and prevented further attempts to generate conformers in it.
Exploration of angular orientation space
Exhaustive exploration
The exhaustive search is one available method for exploration of phase space. We begin
the search by putting the starting structure in standard orientation. We subdivide the
accessible pitch-yaw-roll space into a rectangular array of contiguous cubes15° wide in
each of the three angular directions. A given cube is taken to be sampled if it contains at
least one generated conformer.
If we have a fitness function, though, we can minimize on it as we describe below, rather
than exploring exhaustively.
Line search minimization
For the holo structure prediction application, we chose to minimize the fitness function
using the line search algorithm, which successively varies each of the parameters (pitch,
yaw, roll) over its full range. After each parameter is varied, the conformer that
minimized the scoring function over that parameter is used as a starting point for the next
minimization. This is illustrated in figure 5.3. The line search minimization can be
considered converged when no pitch,yaw, or roll rotation from the lowest-scoring
conformer can further reduce the value of the fitness function.
251