Chemistry Reference
In-Depth Information
Lennard-Jones equations are used to calculate van der Waals interactions whereas
parameters are determined for each atom type with joint interactions determined
by combining rules. It is noteworthy that there is significant effect on hydration
free energies for even small differences in Lennard Jones terms. It is also known
that the electrostatic interactions are larger and can depend on our calculations of
the dielectrics.
Point charges, often used, are approximations involving the electrostatic
interactions between atoms. Models for traditional net atomic charges can be
unsatisfactory for representing molecular electric potential for some systems.
Small changes/perturbations of partial charges can yield significant differences in
calculated free energies of binding or hydration. There is thus a difficulty in
determining the errors in calculated electrostatic energies. It is even more difficult
to estimate the errors in charge transfer.
Regarding intramolecular force field terms (bond stretching, angle bending) some
molecules will have torsions that climb up the potential well. These can be
complex and difficult to duplicate with analytical functions (yielding errors
difficult to estimate). It is impressive how force fields can duplicate the
conformation and structure of isolated small molecules
in vacuo
and how they
drive molecular dynamics simulations to duplicate and maintain biological
systems.
Actually, there are not too many ways to pack connected atoms (by strong bond
stretching and angle-bonding forces). Although we can reproduce many aspects of
bio molecular structure, the information is less than that for small molecule crystal
structure.
What are the consequences of molecular conformations from MD simulations?
Biological motions of proteins appear governed by a large number of multiple
rotors and inter-atomic interactions. The minimum of a conformational well is
easier to determine than its shape. The error in force field may not make it
possible to determine energies at the precision we need.
Considering the simplicity, regarding quantum mechanics, force fields perform
admirable. A good answer is one given with an estimation of confidence.
