Fundamentals of Medicinal Chemistry

Water

Step 1: the selection of the
structure fragments from the
database of the INSIGHT II
program. The molecule with
the relevant functional group
and/or structure is selected.

Step 3: the force field of the model is
minimized to give the final structure.

Step 2: The fragments are linked
together. Fragments are joined to
each other by removing hydrogen
atoms (See shaded boxes in step 1)
at the points at which the fragments
are to be linked. The bonding state of
each atom is checked and, if necessary
adjusted.

HO NHCOCH 3

O H

H

H

H

N

H

H

H

O

C

H

H

H

H C

The INSIGHT II
models of these
structures.

HH

H

H H

H

Benzene Ammonia Methanal Methane

Figure 5.5 An outline of the steps involved using INSIGHT II to produce a stick model of the

structure of paracetamol

atomic coordinates of the model to give a minimum value forETotal. As a result

of this change, the structure on the monitor screen assumes a conformation

corresponding to a minimum energy state. This conformation may be presented

in a number of formats depending on the requirements of the modeller (see

Figure 5.1 and Figure 5.3(a)–(c) ).

The energy minimizing procedure also automatically twists the molecule to

allow for steric hindrance. However, the energy minimizing process is not

usually very sophisticated. It stops when the force field reaches the nearest

local minimum energy value even though this value is not necessarily the lowest

minimum energy value for the structure (Figure 5.6).

MOLECULAR MECHANICS 103