3.6 Base Pair Analysis
Alongside the monomers, we have also built up GC base pair systems consisting of the monomer nucleotides (base-cytosine) with the proposed modifications, in order to observe their base pairing patterns upon base pairing with their complementary nucleobases (guanine). Optimized structures of all the base pairs have been presented in Figure 8. As seen in Figure 8, the monomers were seen to pair quite well with their complementary bases forming three individual H-bond interactions as observed in normal GC base pair. The inter-strand H-bond distances along with intra-strand O3’-P distances for all the modifications have been listed in the Supplementary Table S11. The inter-strand H-bond distances for all the modifications were observed to fall within the range of ~1.8 Å to ~1.9 Å. The distance between the O3’ and P atoms was ~5 Å for the base pairs RC,RCS, LCC, LCS, CME and CMS. This distance was observed to be around ~5.6 Å for the DC and DCS modifications. Whereas, the proposed modifications A1-A5 laid within a range of ~4.8Å to ~5Å. The lower values of intra-strand O3’ and P distances are a property of C3′ endo sugar puckering which were seen in A-type conformation and higher values which are known to be the property of C2′ endo sugar puckering were observed in B-type conformation. Apart from DC and DCS which are supposed to have C2′ endo sugar puckering, all the other modifications showed comparatively lower values for the intra-strand O3’ and P distances. This suggests that these modifications were maintaining a C3′ endo sugar puckering to be an A-type conformation.
The parameters like electronic energy, dipole moment, polarizability, thermal energy, and heat capacity for all the base pairs have been given in the Supplementary Table S12. The pair wise polarity of the A2-G base pair was found to be the lowest (~6.94D) and highest for the A4-G base pair (~12.68D) in all the modifications. The other base pairs all were observed to have intermediate values ranging from ~8D to ~11D. The pairwise polarizability values were found to be the highest for CMS-G base pair and lowest for DC-G base pair. The values of the calculated quantum chemical parameters such as the energy of highest occupied molecular orbital (EHOMO), the energy of the lowest unoccupied molecular orbital (ELUMO), HOMO-LUMO energy gap (ΔEGap), ionization potential (I), electron affinity (A), global hardness (η), global softness (S), chemical potential (μ), and electrophilicity index (ω) are presented in Supplementary Table S13. Observing the HOMO and LUMO energies, it was observed that all the proposed modified base pairs (A1-A5) are having the similar values for differences in their LUMO-HOMO energies compared to the standard and already established residues.
To further evaluate the stability of the base pairs we have calculated the binding energies of the base pairs involved. The electronic energies of the base pairs, individual bases post base pairing and their binding energies all have been listed in Table 6. All the proposed modifications had similar binding energies as the standard residues ie. DC and RC. This along with their negative values for the binding energies suggest stable base pairing for the proposed modifications exhibiting similar kind base pairing patterns compared to the standard base pairs.
Thus a brief analysis on the GC base pairs has helped us to understand the extent to which our proposed modifications were stable on holding the two bases together and that they were capable of complementary base pairing forming standard Watson-Crick base pairing which can form right handed double helix structures when incorporated into oligomer duplexes.