The assessment of molecular dynamics results of three-dimensional RNA aptamer structure prediction

Abstract

Aptamers are single-stranded DNA or RNA that bind to specific targets such as proteins, thus having similar characteristics to antibodies. It can be synthesized at a lower cost, with no batch-to-batch variations, and is easier to modify chemically than antibodies, thus potentially being used as therapeutic and biosensing agents. The current method for RNA aptamer identification in vitro uses the SELEX method, which is considered inefficient due to its complex process. Computational models of aptamers have been used to predict and study the molecular interaction of modified aptamers to improve affinity. In this study, we generated three-dimensional models of five RNA aptamers from their sequence using mFold, RNAComposer web server, and molecular dynamics simulation. The model structures were then evaluated and compared with the experimentally determined structures. This study showed that the combination of mFold, RNAComposer, and molecular dynamics simulation could generate 14-16, 28, or 29 nucleotides length of 3D RNA aptamer with similar geometry and topology to the experimentally determined structures. The non-canonical basepair structure of the aptamer loop was formed through the MD simulation, which also improved the three-dimensional RNA aptamers model. Clustering analysis was recommended to choose the more representative model.

Structural Insights into Protein–Aptamer Recognitions Emerged from Experimental and Computational Studies

“…Taking into account the wealth of information provided by computational studies performed in this field [147,148], this gap of information could be filled by systematically investigating the intrinsic structural/dynamics in the unbound state of the aptamers whose structure complexed with proteins is available. Studies of this type conducted on the aptamers targeting the ribosomal S8 protein [143] or NF-κB [144] demonstrated that protein-aptamer recognition may rely on different mechanisms, i.e., induced fit or population selection.…”

Insights on the comparative affinity of ribonucleic acids with plant-based beta carboline alkaloid, harmine: Spectroscopic, calorimetric and computational evaluation

“…Both NVT and NPT equilibrations were performed for 1ns each followed by a production run of 100ns for all complexes [ [74] , [75] , [76] , [77] ]. The simulations were performed on the set parameters of 298K temperature and 1.02 atm pressure using CHARMM36 force fields [ [78] , [79] , [80] , [81] ]. Despite its limitations, CHARMM36 remains one of the most reliable force fields available for RNA simulations [ [78] , [79] , [80] , [81] ], making it a suitable choice for our study.…”

“…The simulations were performed on the set parameters of 298K temperature and 1.02 atm pressure using CHARMM36 force fields [ [78] , [79] , [80] , [81] ]. Despite its limitations, CHARMM36 remains one of the most reliable force fields available for RNA simulations [ [78] , [79] , [80] , [81] ], making it a suitable choice for our study. Analysis of all trajectories including RMSD, Rg and Bonds were evaluated on VMD 1.9.3 software [ 82 ].…”