To analyze the origin of these different interaction behavior, we have probed further into the mode of interaction of arginine by analyzing the bound minima through three structural parts of arginine: (i) C-alpha (ii) alkyl (iii) guanidinium, as shown in the Fig. . From Fig. , we observe that C-alpha part of the L-arginine is close to the sugar-backbone junction of the RNA. This structural orientation provides the most favorable direction of nucleophilic interaction between the hydroxyl sugar part of RNA and the C-alpha region of the arginine. The similar type of observation was previously reported for trans-acylation reaction between the RNA motif and acylated L-amino acids indicating the favorable geometry for the nucleophilic attack between the hydroxyl group of sugar backbone and the carbonyl group of C-alpha terminal of L-amino acids. A representation of this favorable interaction is shown in the In the context of the above discussion, we find that the two minima in the free energy surface of D-arginine binding to RNA correspond to two different types of stabilizing interactions. In the minima A, (Fig. ), the guanidium part of the arginine is found to form stacking interactions with terminal Cytosine base (residue 12) at the 3' end of RNA. At the same time the C-alpha part of arginine is found to stabilize the complementary base guanine (residue 1) by forming the stabilizing interactions between the carboxylate group in c-alpha part and amino terminal in the Guanine base part. It is important to note that the similar guanidium-nucleobase interaction was found to be very relevant in monitoring the specificity of between D-arginine, and L-arginine as discussed in the literature. It is to be noted that the orientation in of D-arginine is aligned in such a way that the carboxylate group faces towards the nucleobase, increasing the binding affinity. We have inverted the stereochemistry at this stereo center to observe what might have prevented the L-arginine to form the similar binding mode. We have observed that the mirror image L-arginine, the carboxylate part of c-alpha group will be facing against the direction of RNA, failing to form the stabilizing interactions at the c-alpha end, as shown in the Fig. . These orientational effect also reflected in the difference in the interaction energies between the terminal residues of RNA and polar ends of the enantiomers, specifically the aminocarboxylate interactions. A comparison of interaction energy profiles is shown in the Table , supporting the structural observations. Since the stabilizing stacking interactions of D-arginine (and not for L-arginine) was found with the terminal base pair of the RNA, it was assumed that this interaction would prevent the initiation of unfolding in RNA.