Computer-Aided aptamer design for sulfadimethoxine antibiotic: step by step mutation based on MD simulation approach

Area of Science:

• Computational chemistry
• Biotechnology
• Molecular modeling

Background:

• Aptamers are crucial for targeted molecular recognition.
• Existing aptamers may lack optimal binding affinity and specificity.
• Computational design offers a pathway to engineer superior aptamers.

Purpose of the Study:

• To develop a computational method for designing high-affinity aptamers.
• To engineer a mutant aptamer with enhanced specificity for sulfadimethoxine (SDM).
• To validate the designed aptamer's selectivity through simulations.

Main Methods:

• Step-by-step mutation guided by molecular dynamics (MD) simulations.
• Calculation of conformational factor (Pi) to assess residue-target affinity.
• Iterative nucleotide exchange based on Pi values and binding Gibbs free energy (ΔGBind) calculations.

Main Results:

• The M5 mutant aptamer exhibited a substantial increase in binding affinity for SDM (ΔGBind difference of 579.856 kJ/mol).
• MD simulations confirmed the enhanced specificity of the M5 aptamer for SDM.
• The designed aptamer showed selectivity against common interfering compounds.

Conclusions:

• The proposed computational strategy effectively designs aptamers with improved specificity.
• The M5 mutant aptamer is a promising candidate for experimental validation in SDM detection.
• This method provides a powerful tool for aptamer engineering.