Hydration structue of human lysozyme investigated by molecular dynamics simulation and cryogenic X-ray crystal structue analyses:on the correlation between crystal water sites,solvent density,and solvent dipole

摘要

The hydration structure of human lysozyme was studied with cryogenic X-ray diffraction experiment and molecular dynamics simulations.The crystalstructue analysis at a resolution of 1.4 A provided 405 crystal water molecules around the enzyme.In the simulations at 300K,the crystal structure was immersed in explicit water molecules.We examined correlations between crystal water sites and two physical quantities calculated from the 1-ns simulatintrajectories;te solvent density reflecting the time-averaged distribution of water molecules,and the solvent dipole measuring the orientational ordering of water moelcules around the enzyme.The local high solvent densitysites were consistent with the crystal water sites,and better correlation was observed around surface residues with smaller conformational fluctuations during the simulations.Solvent dipoles around thsoe sites exhibited coherent and persistent ordering,indicating that the hydration water molecules at the crystal waer sites were highly oriented through the interactions with hydrophilic residues.Those water molecules restrained the orientational motions of adjoining water molecules and induced a solvent dipole field,which was persistant during the simulations around the enzyme.The coherent ordering was particularly prominent in and around the active site cleft of the enzyme.Because the ordering was significant up to the third to fourth solvent alyer region from the enzyme surface,te coherently ordered solvent dipoles likely contributed to the moelcular recognition of the enzyme in a long-distance range.Thepresent work may provide a new approach combining computational and the experimental studies to understand protein hydration.'