Antibody Structure and Surface Properties
Molecular operating environment (MOE) from Chemical Computing Group
(Montreal, Canada) (Maier & Labute), was used to generate homology
models of three antibodies (referred to here as mAb-1, mAb-2, and
mAb-3). The isoelectric point (pI), percent surface area distribution of
hydrophobic and electrostatic surface properties (positive and negative
patches) were calculated. Patch analysis of these molecules indicate
that the total patches of the molecules are relatively constant (Table
1). Yet, the patch distribution for the complementary determining region
(CDR) varied amongst the three molecules (Table 1). This aligns with the
fact that the constant regions of the molecules are 98% identical. The
variability of the target antigen and recognition site accounts for the
diversity in the CDR region, even though it forms a small fraction of
the entire molecule (approximately 10%). Thus, any variations between
the molecules resulting from the CDR are diminished when averaged over
the entire molecule (e.g. pI). This effectively masks the specific
contribution of the CDR to chromatographic retention and separation if
their contribution is not decoupled from the entire molecule (Figure 1).