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).