Computational Approaches in the Design of Synthetic Receptors - Designing Receptors for the Next Generation of Biosensors - page 134

3. Rational approaches that involve computation of total energies ( E ), energy
differences (DE), and distances ( d ) of closest approach between the monomers
and template using molecular dynamics [ 65 ]
4. The use of density functional theory (DFT) method to calculate the binding
energy

E between a template and monomers as a measure of their interaction
that facilitates the selection of the monomers [ 66 , 67 ]
5. Rational design that involve conformation of template-functional monomer
complexes employing semiempirical methods [ 68 - 73 ]
6. Chemometric approaches to optimizing monomer, template, and cross-linker
ratios [ 74 ]
7. Predicting template:monomer complexes using neural network methods [ 75 , 76 ]

D

The following sections discuss each of the above-mentioned computational
methods for the rational design of MIPs. Table 1 summarizes the different compu-
tational procedures adopted for the rational design of MIPs for a variety of
templates, analysis of polymer properties, and performance of the MIPs.

2 Computational Methods for Rational Design of MIPs

2.1 Rational Approaches That Involve Molecular Mechanics

One of the most established rational approaches in the design of imprinted polymers
is combinatorial synthesis/screening [ 56 , 59 ]. However the combinatorial approach
has its limitations, such that a simple two-component system utilizing 100
monomers would require the preparation of several thousand polymers and even
then would not take into account the possible different ratios of monomer mixtures.
One potential solution to the problem of rational design of polymer lies in molecu-
lar modeling and performing thermodynamic computations using a patented proto-
col developed at Cranfield University [ 61 ]. Variations of this protocol are in use
nowadays in many laboratories around the world.
When there is the requirement to perform structural analysis in large molecular
systems, comprising hundreds of molecules, there is an inherently heavy demand on
computational time and resources. In these cases, molecular mechanics (MM) is
used. MM refers to a system that can be used for qualitative descriptions that
include only potential energy which is essentially devoid of any quantum mechani-
cal calculations. To facilitate calculations, MM considers atoms as balls of certain
radius and the bonds between them as string. The exact values of atom sizes and
bond geometry and strength originate from empirical data collected from X-ray
crystallography and NMR experiments. Several MM software packages exist for a
variety of general and specific applications. Some of the most widely used are
AMBER, MOE, RasMol, QMol, Raster 3D, and AGM Build.
However, a major problem associated with the computational design of
imprinted polymers is the difficulty in performing detailed thermodynamic