l - People

coordinate. This phenomenon is known as gimbal lock from its disastrous possible
consequences in aircraft control systems.
Both of these issues can be dealt with by specifying rotations using axis/angle rather than
euler angle matrices. This involves rotating about a single axis which can point in any
direction, not just along the x,y, or z axes.[97] We found this less intuitive for the user
and so simply restrict the pitch rotations to less than 90° in either direction.
Optional equilibration
The preceding rotation step invariably results in unphysical bond lengths and angles in
the boundary between L and M, and often in steric clashes between M and the rest of the
protein and/or ligand. If an equilibrated structure free of steric strain is desired, a
Molecular Dynamics equilibration is performed using the GROMACS mdrun program
for 1000-10000 time steps (2-20 ps). We found that the shorter time was sufficient to
relieve the most significant steric strains, and the longer time was sufficient to allow an
exponential decrease in enthalpy to level off (data not shown), indicating a better
equilibrated structure. It was not sufficient time to allow substantial domain motions.
Note that equilibration significantly increased the accuracy of ligand-binding prediction,
so including it is recommended for that application.
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