computer modeling in molecular biology.pdf

80 Shoshana .I Wodak, Daniel van Belle, and Martine Prtfvost4.2.3 Structural and Dynamic Propertiesof Water Molecules Near the Protein SurfaceMD simulations can provide a very accurate picture of the structure and dynamicsof water molecules near the protein surface. A number of recent simulation studies[26, 64-66] have already contributed to changing our view from that, provided byX-ray and neutron diffraction studies, where hundreds of molecules are consideredto be statically bound to the protein, to that in which water at the protein surfaceconserves a significant degree of mobility, implying that many fewer watermolecules, if any, are truly immobilized at the protein surface. A similar picture isemerging from experimental analyses by NMR [67-691.4.2.3.1 Structural PropertiesHere we describe results of the analysis of water structure at the surface of barnaseas seen in our 250 ps simulation. Radial distribution function of water oxygens andhydrogens around specific protein atoms in non-polar, polar and charged groupshave been computed in sidechains whose atoms are exposed to solvent [51]. A sampleof these distributions is shown in Figure 4-12a-c.We see that for polar groups, the maxima of the distributions, which correspondto the most probable position of nearest hydrogen bonding partners, are within theexpected hydrogen bonding distances of the groups involved (see fe Figure 4-12a).The peak in the water oxygen distribution around the non-polar methyl group ofAla 32 in barnase (Figure 4-12c) occurs at 3.55 A, corresponding roughly to the sumof the van der Waals radii of the methyl and water groups. Similar distances of 3.6and 3.7 A were obtained previously for the methane-water first peak [70] and forboth the butane-water [71] and the peptide methyl-water [72] first peaks, respectively.A quite useful pictorial representation of the first solvation shell around specificprotein sidechain groups can be obtained by representing water molecules from individualsnapshots along the trajectory in a common local reference frame attachedto the corresponding sidechains, as illustrated in Figure 4-13. Such representation isparticularly helpful in analyzing the water structure in the vicinity of planar groupsas illustrated in Figure 4-13a. This figure shows the near planar arrangement of thewater molecules relative to the aromatic plane of Phe 82 in barnase, with waterhydrogens pointing towards the plane on its more exposed side. In contrast, Figure4-13 b shows the nice spherical arrangement of the water molecules around thesidechain of Ala 32.