Molecular dynamics study of the dissociation of an antigen-antibody complex in solution

Preliminary results are reported of a molecular dynamics calculation of free energy variations during the dissociation of an antigen-antibody complex, hen egg-white lysozyme — Fab D1.3, using atomic coordinates determined by the group of R. J. Poljak, and explicit handling of solvent molecules. After equilibration of the complex in solution at 300 K, a dissociation path was generated by a directed dynamics protocol. Then the thermodynamic perturbation method was used for computing the derivative of the free energy of the system with respect to dissociation coordinate, both for the undissociated complex and in two points along the path. 200-ps molecular dynamics simulations were carried out at each of these points. The results obtained are discussed, with special emphasis on the role of interstitial water in the appearance of a hydrophobic activation free energy.Université Paul Sabatier, and URA 505 of C.N.R.S.