Small molecule crystal structures

Small molecule crystal structures solved through direct methods yield very accurate atomic positions... 

The great majority of Ca ligands in small-molecule crystal structures are oxygen atoms. In protein crystal structures oxygen atoms are the only Ca ligands observed to date. Of the 182 ligands in the 27 sites of Table... 

Maass, P., Schulz-Gasch, T., Stahl, M., Rarey, M. (2007) ReCore a fast and versatile method for scaffold hopping based on small molecule crystal structure conformations. J Chem Inf Model 47(2), 390-9. 

The Cambridge Structural Database is a repository for more than 250000 (as of 2002) small molecule crystal structures. It is accessible at http // www.ccdc.cam.ac.uk/ by subscription. 

The Cambridge Crystallographic Data Centre produces the Cambridge Structural Database (http //www.ccdc.cam.ac.uk/products/csd/), which covers organic and metal-organic small-molecule crystal structures. 

Significance of Small Molecule Crystal Structural Studies... 

The Problems of Measuring Hydrogen-Bond Lengths and Angles in Small Molecule Crystal Structures... 

As in the small molecule crystal structures the water molecules are three- and four-coordinated (see Part IV, Chap. 21). 

This procedure is comparable to that used to analyze the N-H 0=C interactions in small molecule crystal structures described in Part I A, Chapter 2.3 [75]. For those groups with rotational freedom such as the -OH in serine, threonine, and tyrosine, the S-H in cysteine, and the - +NH3 in lysine and at the amino terminus, it is more difficult to guess the likely position of the hydrogen atoms. In these instances, the assumptions are made that the hydrogen bonds are of the two-center type when the R-X - A angle is close to 110°. The bonds are assumed to be linear with X-ft A angles of 180° (a better approximation would be to take the most commonly observed angle of —160°). 

Because internal water molecules are in mostly apolar environments, their hydrogen bonds are often strong and well defined. The average O- -O distance is 2.89 0.21 A for the internal water molecules in lysozyme, carboxypeptidase, cytochrome c, actinidin, and penicillopepsin. As with the small molecule crystal structures, the water molecules are involved in three or four hydrogen bonds, with 48% engaged in three and 37% in four interactions. 

An alternate interpretation is that hydrogen bonding is dynamic and that the water molecule is satisfying all acceptor sites by rotating into two positions [596]. A distinction between these two hypotheses is difficult for small molecule crystal structures, and impossible for proteins. 

In protein X-ray structure determinations hydrogen atoms cannot be located, and their positions have to be calculated from the known coordinates of the C, N, O atoms. Their positions are an order of magnitude less well defined than with small molecule crystal structures. Nevertheless, general trends can be derived and yield valuable information. 

In the peptide bond, y can have positive and negative values because the Ca atoms distinguish between each side of the peptide plane. This is not so in the small molecule survey where a number of different types of molecules were considered. Therefore, absolute values should be compared, 18(9)° in proteins and 30° to 80° in small molecule crystal structures. 

As we have seen in the previous Section 19.6, secondary-structure hydrogen-bonding geometry in the a-helices, / -pleated sheets and / -turns is constrained by the requirements of polypeptide chain folding. When the hydrogen bonds which are not involved in secondary-structure interactions are examined, their geometry is in better agreement to that observed in the small molecule crystal structures discussed in Part IB, Chapter 7. In most cases, therefore, the discussion can be limited to situations where deviations occur [596]. 

As observed for the N- H O interactions between main-chain and side-chain groups, the N-ft Ow angles are almost linear, 156(15)°, if the all-a-helix proteins are omitted from the sampling, see Ihble 19.6d. The distribution of these angles is 140° to 180° for 90% of the data, and consistent also with small molecule crystal structures [75, 382, 475]. The spread of hydrogen-bond distances is broad, and wider for C=0 than for N-H, probably because the C=0 oxygen is more readily accessible and multiple C=0- -HOw interactions are frequently observed. 

In contrast to small molecule crystal structures, where the variation in most H A distances falls within 0.3 A, hydrogen-bonding distances involving side-... 

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