The method of molecular mechanics with an AMBER 3.0 computer software package, supplemented by specially developed subprograms, was used to carry out a conformational analysis of hybrid double helices with noncanonical H-bonds composed of oligodeoxyribonucleotide and oligoamide fragments (dT)₅ · (pT)₅ (1) and (dA)₄(dT)₂(dA)₄ · (dT)₃(pT)₄(dT)₃ (2). The purpose of the work was to perform a pre-synthesis estimation of Watson—Crick specificity of binding specially constructed oligomers, which carry oligoamide inserts of 2-aminoethylglycine units in the center, connected to nitrogen bases through a methylenecarbonyl group. A comparison of helical parameters and potential energies in optimized structures of hybrid oligonucleotides with noncanonical T · T-pairs with the energies of analogs containing only canonical A · T-pairs showed that disruption of Watson—Crick complementarity results in a crucial distortion of hybrid double helices, which leads to their destabilization. For this reason, the expected probability of mispairing of oligonucleotides is low for the proposed analogs of oligonucleotides carrying oligoamide inserts. Hence, the synthesis of these oligonucleotides is promising for creating reagents with selective action on single-stranded oligonucleotides inside cells.