Biophys J, December 2000, p. 2954-2965, Vol. 79, No. 6

Kinetics of Association of Anti-lysozyme Monoclonal Antibody D44.1 and Hen-Egg Lysozyme

Gioia Altobelli^* and Shankar Subramaniam^*

 ^*National Center for Supercomputing Applications,  Center for Biophysics and Computational Biology, Departments of Biochemistry, Molecular & Integrative Physiology and Chemical Engineering and Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, Urbana Illinois, 61801, and  Departments of Bioengineering and Chemistry and Biochemistry, University of California at San Diego, La Jolla, California 92093 USA

Association rate constants for antigen/antibody associations have been computed by Brownian Dynamics simulations of D. L. Ermak and J. A. McCammon, J. Chem. Phys. 69:1352-1360, 1978. The model of monoclonal antibody (mAb) D44.1 is based on crystallographic data (B. C. Braden et al., J. Mol. Biol. 243:767-781, 1994). Electrostatic forces that steer the antigen to the antibody-combining site are computed by solving the linearized Poisson-Boltzmann equation. D44.1-HEL complex displays very similar association motifs to a related anti-lysozyme antibody, HyHEL-5-HEL system. The computed association rate constants are comparable in the two systems, although the experimental affinity constants differ by three orders of magnitude (D. Tello et al., Biochem. Soc. Trans. 21:943-946, 1993; K. A. Hibbits et al., Biochemistry. 33:3584-3590, 1994). Simulations suggest that the origin of the differences in the affinity come from dissociation rate constants. We have also carried out simulation experiments on a number of mutant antibody fragment-HEL associations to address the role of electrostatics and, to a limited extent, the orientational aspects of association.

Biophys J, December 2000, p. 2954-2965, Vol. 79, No. 6
© 2000 by the Biophysical Society   0006-3495/00/12/2954/12  $2.00

This article has been cited by other articles:

				W. Swegat, J. Schlitter, P. Kruger, and A. Wollmer MD Simulation of Protein-Ligand Interaction: Formation and Dissociation of an Insulin-Phenol Complex Biophys. J., March 1, 2003; 84(3): 1493 - 1506. [Abstract] [Full Text] [PDF]