Side-chain geometries

Optimal amino acid side-chain geometries must be taken into account in... 

Theoretically there are 20 x 20 = 400 possible different combinations of amino acid residues adjacent to one another in a polypeptide. If each possible combination needed a specific protease, then 400 different proteolytic enzymes would be required. However, the proteolytic enzymes have broad specificities, largely confined to groups of amino acids with similar side chain geometries, and therefore only a few different types of enzyme are encountered. 

The different contributions to conformational energy by noncovalent interactions mentioned previously impose severe restrictions for the folding of a polypeptide chain. One must consider restrictions in backbone folding (0i, side chains geometry (xf). 

Levitt Warshel [17, 18] were the first to show that reduced representations may work they used Ca atoms and virtual atoms at side chain centroids. OOBATAKE Crippen [24] simplified further by only considering the Ca atoms. This is snfficient since there are reasonably reliable methods (Holm Sander [11, 12]) that compute a full atom geometry from the geometry of the Ca atoms. (All atom representations are used as well, but limited to the prediction of tiny systems such as enkephalin.)... 

In systems of proper geometry, nucleophiles within a side chain may be well connected for attack on ring atoms. For example, an aminomethyl group at the 5-position of a dibenzazepine-2-one was found to attack the carbonyl group (Section 5.16.3.5.2). Such reactions should be possible in rings of any size. 

The proteins thus adapt to mutations of buried residues by changing their overall structure, which in the globins involves movements of entire a helices relative to each other. The structure of loop regions changes so that the movement of one a helix is not transmitted to the rest of the structure. Only movements that preserve the geometry of the heme pocket are accepted. Mutations that cause such structural shifts are tolerated because many different combinations of side chains can produce well-packed helix-helix interfaces of similar but not identical geometry and because the shifts are coupled so that the geometry of the active site is retained. 

In both structures the ion is coordinated to six ligands with octahedral geometry. Four water molecules as well as the side chain oxygen atom of a serine residue from the P-loop and one oxygen atom from the (3-phosphate bind to Mg + in the GDP structure. Two of the water molecules are replaced in the GTP structure by a threonine residue from switch I and an oxygen atom from the y phosphate (similar to the arrangement shown in... 

British Biotech has described co-crystal structures of both BB-3497 and actinonin bound in the active site of E. coli PDF [24]. The metal centre (Ni ) in both complexes adopts a pentacoordinate geometry, bound by the two oxygen atoms of the hydroxamate along with Cys-90, His-132 and His-136. This coordination pattern is consistent with the mechanism of de-formylation proposed by Becker et al. [56] and Jain et al. [67], in which a pentacoordinated metal centre stabilises the transition state during hydrolysis of the formamide bond. When compared to the co-crystal structure of a substrate hydrolysis product, Met-Ala-Ser, it is clear that the side chains of these two inhibitors bind into the active site pockets similarly to the substrate [56]. 

Consequently, the signal fractions of 51 f(r)/51 f(0) can be calculated and compared with simulations. For samples prepared by bacterial expression, correction of the background signals can be carried out in a similar fashion [48, 53, 54], It is noteworthy that spin geometries deviated from linearity, which may occur in the side-chain 13C nuclei such as C , would produce more rapid signal decays and smaller residual signal fraction [55],... 

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