In‐silico selection employing rigid docking and molecular dynamic simulation in selecting DNA aptamers against androgen receptor

Abstract

Aptamers are a class of single‐stranded (ss) nucleic acid molecules generated through Systematic Evolution of Ligands by Exponential Enrichment (SELEX) that involves iterations of time‐consuming and tedious selection, amplification, and enrichment steps. To compensate for the drawbacks of conventional SELEX, we have devised an in‐silico methodology that facilitates a cost‐effective and facile manner of aptamer selection. Here, we report the isolation of DNA aptamers against androgen receptors (ARs) using androgen response elements (ARE) that possess natural affinity toward AR. A virtual library of ARE sequences was prepared and subjected to a stringent selection criterion to generate a sequence pool having stable hairpin conformations and high GC content. The 3D‐structures of the selected ss AREs were modeled and screened through rigid docking and molecular dynamic (MD) simulation to examine their potency as potential AR binders. The predicted sequences were further validated using direct enzyme‐linked aptasorbent assay (ELASA), which includes the measurement of their binding affinity, specificity, and target discrimination properties under complex biological enviroments. A short, 15 nucleotides (nts), ssDNA aptamer, termed ARapt1 with the estimated Kd value of 5.5 ± 3 nm, was chosen as the most prominent aptamer against AR based on the coherence of both the in‐silico and in‐vitro evaluation results. The high target‐binding affinity and selectivity of ARapt1 signify its potential use as a versatile tool in diagnostic applications relevant to prostate cancer and related diseases.

H‐Bond Modulation Mechanism for Moisture‐driven Bacteriostat Evolved from Phytochemical Formulation

“…The most favorable docking result with the lowest free energy is shown in Figure 2C. According to the simulation mode, [38,39] vanillin molecule implanting into 𝛾-CD-MOF cavity had the intermolecular energy of −6.01 kcal mol −1 . In particular, hydroxyl hydrogen of 𝛾-CD binding with the carbonyl oxygen of vanillin formed a H-bond with a bond length of 1.9 Å, which was the preferential binding pattern of host-guest structure in 𝛾-CD-MOF@Van formulation.…”