computer modeling in molecular biology.pdf

116 E. WesthoJ C. Rubin-Carrez, and K Fritsch5.9 Choice of CounterionsThe importance of ions for the stabilization of deoxy- and ribonucleic acids, has longbeen recognized. The theoretical treatment of specific ion binding is difficult. Whendiscussing metal ion binding to nucleotide ligands two limiting cases are usually considered:(a) site binding with a direct coordination of the metal ion to ligands of thenucleotide, leading to the formation of inner-sphere complexes after partial dehydrationof the metal ion; (b) ion atmosphere binding wherein the metal ions with theirintact hydration shells interact indirectly through water molecules with thenucleotides, forming outer-sphere complexes [30]. The kinetics of magnesium bindingto polynucleotides have been well studied 1311 and follow the preceding structuraldescription. First, an outer-sphere complex is formed with a rate close to thelimit of diffusion control. In a second step, one or more water molecules exchangewith ligand of the polynucleotide leading to inner-sphere complexation with a ratedetermined by the process of water dissociation, around 100000 per second formagnesium and 1000 times faster for calcium ions. The second step was observedonly with short oligoriboadenylates, indicating that inner-sphere complexation requiresparticular conformations of the nucleotide chains and the presence of theadenine base and of the ribose hydroxyl group 02’.nYo features observed in crystal structures appear interesting [lo] (Figure 5-7).First, the ion is rarely bound directly to the phosphate anionic oxygen atoms inribonucleotide complexes, but more often in deoxynucleotide complexes. Direct contactto nucleic acid ligands occur mainly at N7 of purines and at anionic oxygenatoms while fully hydrated ions interact as often with the bases as with the sugarphosphatebackbone. Secondly, often one or two water molecules of the ion hydrationshell are common to two ions so that they share an apex or an edge of the coordinationspheres (two such sodium ions are separated by 3.3 to 3.8 A). While watermolecules are weakly held to sodium ions (they exchange at the diffusion-controlledvalue and have thus residency times on the ion around the nanosecond), watermolecules are held more strongly to magnesium ions. The very high rate constantsfor magnesium ions association to polynucleotides indicate “outer sphere” complexation.Therefore, not surprisingly, crystal structures of nucleotides and polynucleotidesreveal “inner sphere” complexation with sodium ions and “outersphere” complexation with magnesium ions. However, while magnesium binding tobases in helices appears to be preferentially of the “outer sphere” type, binding tophosphate groups occur in loops and bends of the sugar-phophate backbone and isoften of the “inner sphere” type.As counterions, we have favored the use of ammonium ions. First, its tetrahedralstereochemistry resembles that of water and its geometry as well as its empiricalparameters have been determined [32]. Secondly, as described above, other types ofcounterions possess coordinated water molecules (e. g. the octahedral arrangement