MOLECULAR-DYNAMICS STUDY OF THE HYDRATION STRUCTURE OF AN ANTIGEN-ANTIBODY COMPLEX

Molecular dynamics simulations of the hen egg-white lysozyme-Fab D1.3 complex were performed, starting from the X-ray crystallographic coord inates obtained by Fischmann et al. [J. Biol. Chem. 1991, 266, 12915-1 2920], and including counterions and explicit random water molecules. Both the crystal state and the complex in solution were studied, the f ormer as the asymmetric unit cell in interaction with all its neighbor s, and the latter with a new model (the ''egg'') consisting of a trunc ated ellipsoid containing the complex and solvent molecules, a first s hell with additional solvent, and two further shells with virtual solv ent molecules derived from those of the first shell by a geometrical c orrespondence. The hydration structure of the complex is analyzed from the data obtained after equilibration and fluctuation dynamics of the se two systems. The water density around the protein is found to incre ase, up to a maximum of 1.5 for the complex in solution, so that the i ntegrated density largely exceeds unity. Therefore additional water mo lecules were steadily included into the ''egg'' model. In the crystal cell model an average density of unity was conserved. Detailed analyse s are given of the pair correlation functions, coordination numbers, l ocal water density, and orientations of water molecules. Two hydration shells are observed around the complex in solution, the inner one wit h molecular orientations very dependent on the local character of the protein surface (either nonpolar, or positively or negatively charged) , whereas the second shell which extends continuously toward the bulk is essentially homogeneous, apart from slight residual orientational p references of the dipole moments in the first few A of this shell when the closest protein atom is positively or negatively charged. Compari sons of the root-mean-square fluctuations of the protein backbone atom s from the simulations of the complex in the crystal state and in solu tion with experimental B factors from the X-ray crystallographers show the importance of a correct description of the water density around t he protein. It is argued that the absence in the crystal cell of a bul klike aqueous phase may lead to a higher mobility of the protein chain s in the crystal than in solution.