Study of the binding mechanism between aptamer GO18-T-d and gonyautoxin 1/4 by molecular simulation

Abstract

GTX1/4 can induce the formation of an antiparallel G-quadruplex structure in aptamer GO18-T-d and combine steadily in the groove at the top of the G-quadruplex structure. The complex structures and special induced fit mechanism between aptamer and small molecules provide a reference for aptamer development in molecular diagnostics and therapeutic application.

Study of the binding mechanisms between palytoxin and its aptamer by docking and molecular simulation

“…Therefore, as demonstrated in our previous work [17] , the binding site of P-18S2 with G-quadruplex structure was at the top (S5 Fig). Finally, the molecular docking analysis was carried out using Hex 8.0 [34] . Rotation of receptor and ligand was allowed in 180 degree, without the specified binding group.…”

“…At the same time, the interaction mechanism of aptamers with targets still needs further exploration for the therapeutic application of aptamers. In our previous work, we obtained the aptamer(GO18-T-d) [15] of GTX1/4 and analysed the binding mechanism of GTX1/4 and GO18-T-d by a series of molecular modeling programs [17] . In addition, we also obtained the aptamer P18-S2 that can bind to PTX with a high Kd of 0.93 nM [10] by SELEX and Biolayer interferometry (BLI) which is a real-time optical analytical technique for measuring interactions between biomolecule [18] .…”

“…Therefore, we have further truncated and optimized to P-18S2. In addition, this paper further refined research method based on our previous study [17] , the instability of the target structure was considered and optimized, and the biological experiments were used to confirm the veracity of the simulative results. Combining with the experimental and computational methods, we obtained a reasonable interpretation for the high affinity and specific binding of P-18S2 and PTX.…”

The Bound Structures of 17β‐Estradiol‐Binding Aptamers

“…MD can provide insight into the molecular interactions involved in binding, binding affinity, important binding positions, minimal binding sequence, mutations to enhance binding, and the best places to tether newly‐defined aptamers onto electrodes, nanoparticles, nanotubes and dyes. Yet, few computational studies exist investigating aptamer‐target interactions at a molecular level . Aeksiri et al .…”

“…improved understanding of the binding of the thrombin‐binding aptamer using MD simulations. Few MD studies have addressed aptamers binding to small molecular targets, where binding interactions are expected to be very sensitive to precise structures.…”