Metrics of Water Hydrogen Bonding to Proteins

Water molecules are small probes. They can hydrogen-bond to protein functional groups with few steric limitations, in contrast to the hydrogen bonds between protein main-chain and side-chain atoms which have been the topic of Part III, Chapter 19. The hydrogen bonds involving water are therefore considered to reflect the intrinsic hydrogen-bonding properties of a protein. 

Main-chain to water hydrogen bonds. If water molecules hydrogen-bond to the main-chain C=0 groups, they associate preferentially in the direction of the oxygen lone-pair orbitals. This is clearly indicated in Fig. 23.4 a and by the data given 

The main-chain N-ft -Ow angles are approximately linear, 156 15° (Thble 23.5b), with the 90Vo majority in the range 140°-180° (see also Fig. 23.4a). Angles below 140° occur mainly with three-center bonds where one N-H group donates to two acceptors. 

If distances between main-chain C=0 and N-H groups and hydrogen-bonded water molecules are compared (Thble 23.5 and Fig. 23.5 a), it is apparent that the distribution is narrower about the N-H groups. The reason is that the C=0 groups are more exposed and, in most cases, accessible to more than one or two hydrogen-bond donors. Where this results in overcrowding the C=0 0W distances may be beyond the 3.5 A cut-off limit used in the analysis [596]. In the major parts of both C=0 Ow and N-H ow distribution, the peaks in Fig. 23.5a are at 2.89 A (2.94 A in Thble 23.5a) and 2.97 A respectively, as expected from the data for the hydrogen bonds in small molecule crystal structures. 

Nevertheless, some differences are observed from the distance and angle distribution histograms in Fig. 23.5 b and from the stereo views in Fig. 23.4b. In the 

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