Investigation of Carbohydrate Recognition via Computer Simulation

Abstract

Carbohydrate recognition by proteins, such as lectins and other (bio)molecules, can be essential for many biological functions. Recently, interest has arisen due to potential protein and drug design and future bioengineering applications. A quantitative measurement of carbohydrate-protein interaction is thus important for the full characterization of sugar recognition. We focus on the aspect of utilizing computer simulations and biophysical models to evaluate the strength and specificity of carbohydrate recognition in this review. With increasing computational resources, better algorithms and refined modeling parameters, using state-of-the-art supercomputers to calculate the strength of the interaction between molecules has become increasingly mainstream. We review the current state of this technique and its successful applications for studying protein-sugar interactions in recent years.

Figure 1

(a) A three-dimensional representation of a binding pocket of a lectin (2γ site of the ricin B chain). Only the sugar residues and amino acid residues involved in ring-stacking and hydrogen bonding are shown. Hydrogen and backbone atoms are excluded for clarity. (b) A three-dimensional representation of a lectin (ricin chain B, PDB Code 2AAI) with lactoses bound at sites 1α (lower-left) and 2γ (upper-right). (c) A depiction of binding sites 1α and 2γ with possible hydrogen bond and ring stacking residues shown. (d) A three-dimensional representation of the cellulose binding module (CBM) of a CAZyme (Cel7A with cellulose modeled by M. Crowley’s group) (e) Residues of Cel7A’s CBM that interact with cellulose. Cellulose chains are represented by gray stripes on the plane.

Figure 2

Three-dimensional representations of PC1 and PC2 values are shown in (a) and (b), respectively. For clarity, only those contacts with absolute values of >0.05 are explicitly displayed as colored cylinders. Elements in eigenvectors PC1 and PC2 that contain the contact interaction between ligands and the protein complex are show in (c) and (d), respectively.