The aaRSs-tRNA encounter complexes and electrostatic interactions.

For the most part aaRSs are negatively charged at physiological conditions, as also are tRNA substrates. It is apparent that should be found a driving force that ensures an attraction between like-charged aaRS and tRNA, and formation of the close encounters. Our results suggest that non-specific electrostatic interactions are the driving forces for primary stickiness of aaRSs and tRNA, and these are precisely the interactions that control encounter complex formation. Attraction between aaRS and tRNA at long distances (~0.01 kT/e) is due to capture of the negatively charged tRNA molecule by the positive potential of aaRS concentrated in the �blue space� areas (see Figure 1). As it turned out the 3D-isopotential surfaces generated by monomeric, dimeric and heterotetrameric synthetases from both classes reveal the presence of large positive patches (�blue space�), one for each tRNA substrate molecule. However, numerous questions remain to be addressed. We are currently interested in finding correlation between electrostatic fields created by individual structural domains and exerting some action on complex formation and evolutionary pathway of a given protein. It is of interest to model the trajectory of tRNA motion towards the binding site of the aaRSs (Figure 2).

Class I, monomeric ArgRS, same-subunit binding Class II, heterodimeric PheRS, cross-subunit binding

Figure 1. 3D-isopotential surface representation of aaRSs and overall views of their complexes with cognate tRNA: class I monomeric ArgRS (a, b); class II heterotetrameric PheRS (c, d). Pairs of figures 1a and 1b, etc., are displayed in different scale and have equivalent orientation. Structural domains of ArgRS and subunits of PheRS are marked with different colors. The tRNA is shown as blue ribbons. All isopotential surfaces are calculated and built at �0.01 kT/e with GRASP. Patches of positive (+) and negative (-) potentials are shown in blue and red respectively.

Figure 2. The tRNAIle pathway toward the bound state in IleRS-tRNAIle complex. (a) The energetically most favorable position of tRNAIle (red) on the Reactive sphere (RES). The tRNAIle (red) immersed into the reactive patch, determined as the area of positive potential (blue) on RES. The IleRS and tRNAIle in binary complex are colored by green and gold. (b) The binding energy (?Eint) dependence of the center-to-center distance between IleRS and tRNAIle. The ?Eint shows its minimum when the center-to-center distance approaches the RES radius.

Class I, monomeric ArgRS, same-subunit binding	Class II, heterodimeric PheRS, cross-subunit binding

Figure 1. 3D-isopotential surface representation of aaRSs and overall views of their complexes with cognate tRNA: class I monomeric ArgRS (a, b); class II heterotetrameric PheRS (c, d). Pairs of figures 1a and 1b, etc., are displayed in different scale and have equivalent orientation. Structural domains of ArgRS and subunits of PheRS are marked with different colors. The tRNA is shown as blue ribbons. All isopotential surfaces are calculated and built at �0.01 kT/e with GRASP. Patches of positive (+) and negative (-) potentials are shown in blue and red respectively.

Figure 2. The tRNAIle pathway toward the bound state in IleRS-tRNAIle complex. (a) The energetically most favorable position of tRNAIle (red) on the Reactive sphere (RES). The tRNAIle (red) immersed into the reactive patch, determined as the area of positive potential (blue) on RES. The IleRS and tRNAIle in binary complex are colored by green and gold. (b) The binding energy (?Eint) dependence of the center-to-center distance between IleRS and tRNAIle. The ?Eint shows its minimum when the center-to-center distance approaches the RES radius.