See related material in linmin and equilibration . Pre-4.1 EDIT did not do a good job of trimming waters at the faces of the periodic box, so waters could overlap to the point of virtual superimposition at the box boundary. This leads to strong enough forces to blow things apart. As of 4.1 EDIT , .4A 'breathing' room has been added to the box, so this problem should become relatively rare. PBC's, and needless to say it is annoying.
Constant pressure is achieved by changing the box size.
All the coordinates get scaled and then shake has to repair the bond distances. If the scaling is excessive, then shake can't cope. The resulting jump in virial causes major expansion in the box, stretching bonds too far for shake to recover. Solute-solute imaging is turned off. For simulations of highly charged solutes in a water bath, it can be useful to calculate ALL solute - solute nonbonded interactions in order to reduce electrostatic problems.