Interactions between CD44 protein and hyaluronan: insights from the computational study.

CD44 is a protein, being a major cell surface receptor for hyaluronan (HA). Molecular modeling investigation was carried out on the murine CD44 in complex with a HA heptasaccharide in order to: (i) elucidate the nature and dynamics of interactions between the HA chain and CD44; (ii) find out if the existence of two conformational forms of CD44 discovered in the XRD (X-Ray Diffraction) study can be responsible for its switching between low and high affinity for HA. The results indicate that the contact of CD44 with HA is dominated by hydrogen bonding with small contribution of hydrophobic interactions and salt bridges. In addition, the two ('A' and 'B') conformational forms of the HA-CD44 complex reported experimentally by Banerji et al. cannot be observed during simulations when considering the distance between HA and the sidechain of the R45 residue. There exists, however, a free energy barrier associated with the change of the φ dihedral angle value at Y46. Additionally, some thermodynamic parameters (e.g. the Gibbs free energy change) accompanying the HA binding by CD44 were estimated.