The Binding of Citric Acid to Citrate Synthase

Molecular dynamics simulations [69] of citric acid in water at room temperature do show intermolecular hydrogen bonds to the solvent molecules along the entire trajectory [54]. To observe a gauche/trans-transition (T3) within a time-frame of a few 100 ps, the simulation temperature has to be elevated. Computational studies including a molecular environment capable of forming hydrogen bonds clearly are more relevant than gas-phase calculations in the search for biologically active conformations. 

3 Conformation of Guanosine and Adenosine Phosphates in Small-Molecule and Ligand/Protein Crystal Structures 

Given these variances and covariances, the torsion angles T14, T]6, T17, T20 (cf. components 2-5) were selected for a comparison of the conformational preferences of the trial fragment in small molecule crystal structures with those in protein environments [54]. Since torsion angles from protein structures are inaccurate, distances between the centers of the purine and ribose ring, and between these centers and 

7 to 180° and 60°. These findings agree with results of earlier studies [76, 77]. The angle T14 shows the largest differences between protein and small molecule structures. In the latter, the C-C-O-P fragment nearly always occurs in a g-con-formation, while in the protein environment a broad distribution is observed g , (). This is confirmed by the distributions of the distances, cl, d2, and d. Whereas the rf, and di distributions resemble each other in both data sets, the d distributions show clear differences. For the small molecule data, this distance is about 6.5 A in most structures it is larger than 7.5 A in only three of the 90 examples. For the proteins, d clusters at 6.6, 7.8 and 8.8 A. 

The preference of the nucleotide molecules for the folded conformation may be understood from the crystal structure of the lithium salt of NAD [78]. The cation 

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