Methods and Applications of In Silico Aptamer Design and Modeling

Abstract

Aptamers are nucleic acid analogues of antibodies with high affinity to different targets, such as cells, viruses, proteins, inorganic materials, and coenzymes. Empirical approaches allow the design of in vitro aptamers that bind particularly to a target molecule with high affinity and selectivity. Theoretical methods allow significant expansion of the possibilities of aptamer design. In this study, we review theoretical and joint theoretical-experimental studies dedicated to aptamer design and modeling. We consider aptamers with different targets, such as proteins, antibiotics, organophosphates, nucleobases, amino acids, and drugs. During nucleic acid modeling and in silico design, a full set of in silico methods can be applied, such as docking, molecular dynamics (MD), and statistical analysis. The typical modeling workflow starts with structure prediction. Then, docking of target and aptamer is performed. Next, MD simulations are performed, which allows for an evaluation of the stability of aptamer/ligand complexes and determination of the binding energies with higher accuracy. Then, aptamer/ligand interactions are analyzed, and mutations of studied aptamers made. Subsequently, the whole procedure of molecular modeling can be reiterated. Thus, the interactions between aptamers and their ligands are complex and difficult to understand using only experimental approaches. Docking and MD are irreplaceable when aptamers are studied in silico.

Artificial Intelligence in Aptamer–Target Binding Prediction

“…The computational methods provide convenient and accurate ways to select aptamers with high affinity. A typical modeling workflow of aptamer selection by computational methods comprises four steps ( Figure 1 ) [ 11 ]. Firstly, the secondary structures of aptamers are predicted by their sequences.…”

“…After the molecular docking, MD simulations need to be performed to evaluate the stability of protein–aptamer complexes and determine the binding energies [ 11 ]. The typical MD process contains the initial molecular configuration describing the atomic interactions and model physics, running a simulation, and recording observations from the trajectory [ 56 ].…”

“… Typical workflow of in silico aptamer design and analysis. The diagram was adapted from Buglak et al [ 11 ]. …”

“…Recently, some researchers used computational methods to select aptamer candidates because of their convenience and low cost [ 10 , 11 ]. These methods aim at predicting the aptamer affinity toward targets through structural information [ 12 ].…”

BipD of Burkholderia pseudomallei: Structure, Functions, and Detection Methods

“…DNA aptamers are more stable (including in human serum), do not require additional steps such as reverse transcription, and are cost-effective to produce [ 80 , 81 ]. In addition, we also recommend the use of bioinformatics tools and computational methods in aptamer screening and aptamer–target complex identification to overcome the disadvantages of SELEX techniques, which are tedious, time-consuming (usually taking several weeks to complete), and not cost-efficient [ 82 ].…”