Re: CCL:MD/MM combination



 > Let's consider the following example:
 > We have a rather flexible molecule which has functional groups allowing the
 > formation of hydrogen bonds. Now we put it in a box of water molecules and
 > calculate the potential energy of the system with a forcefield. If we do an
 MD
 > calculation with a fixed geometry of the molecule (just the solvent is
 moving)
 > we'll get an ensemble and we can average the potential energy.
 Sure, but I don't see what this "averaged potential energy" is good
 for. It is not a well-defined thermodynamic quantity.
 > Question 2:
 > If I calculate all internal forces on the atoms of the molecule and average
 all
 > forces excerted by the solvent on the molecule, I'll get the gradient on
 that
 > potential energy surface mentioned above. (Right?)
 Not quite. What you described above is the calculation of some energy
 for isolated configurations, not a surface. The average force is (by
 definition) the gradient of the potential of mean force, which is a
 well-defined thermodynamic quantity.
 > Question 3:
 > As far as I understood the Thermodynamic Integration method and related
 > methods, the free energy difference can be calculated by defining a
 reaction
 > coordinate  and integrating over the averaged forces along that reaction
 > coordinate.
 Right, and that will give you the profile of the potential of mean force
 along the reaction coordinate.
 > I'm not quite clear, where this deviates from the aproach above. If I asume
 the
 The difference is that you have to calculate a whole path between two
 configurations, whereas your original idea was to calculate something for
 only the two end points. A separate calculation of the two end points
 means that you have an unknown additive constant for *each* of them,
 and hence no information about the difference in free energy. By calculating
 the path you end up with only *one* unknown additive constant, and you
 can evaluate the energy.
 --
 -------------------------------------------------------------------------------
 Konrad Hinsen                          | E-Mail: hinsen { *at * } ibs.ibs.fr
 Laboratoire de Dynamique Moleculaire   | Tel.: +33-76.88.99.28
 Institut de Biologie Structurale       | Fax:  +33-76.88.54.94
 41, av. des Martyrs                    | Deutsch/Esperanto/English/
 38027 Grenoble Cedex 1, France         | Nederlands/Francais
 -------------------------------------------------------------------------------