Publication: Binding evaluation of truncated aptamer 63 targetting PB2a protein of methicillin-resistant staphylococcus aureus via in silico & electrochemical analysis
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Date
2026-01
Authors
Ruzi, Nurin Maya Hawani Mohd
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Abstract
Methicillin-resistant Staphylococcus aureus (MRSA) is a major global public health concern and one of the leading contributors to antimicrobial resistance linked to approximately 4.95 million deaths worldwide in 2019 and MRSA accounting for over 100,000 deaths directly attributable to resistance. This resistance is largely mediated by penicillin-binding protein 2a (PBP2a), which exhibits low affinity for β-lactam antibiotics and significantly limits effective treatment options. Therefore, a PBP2a-targeting aptamer could be explored as a therapeutic adjuvant to be co-administered with β-lactams to inhibit PBP2a function and restore antibiotic susceptibility. Aptamers have gained increasing attention as an ideal antibody alternative for their high specificity and affinity with various applications such as diagnostic tools and therapeutic agents. However, long aptamer sequences may increase synthesis cost and limit their practical performance. This study aimed to optimize and design from previously reported DNA Aptamer 63, that targets PBP2a through rational truncation while preserving its binding functionality. Truncation was guided based on structural analysis from secondary structure prediction and three-dimensional complex analysis in PyMol. Three truncated variants which are Aptamer 63a, 63b and 63c were evaluated using molecular docking and molecular dynamics simulations. Aptamer with highest stability and compatibility with PBP2a protein was validated electrochemically alongside the original aptamer, and dissociation constants (Kd) were determined to compare binding affinities. This study found that the truncated aptamer derived from Aptamer 63 show no significant improvement in binding affinity toward PBP2a compared to the original aptamer through electrochemical method. Although truncation did not result in improved binding affinity, Aptamer 63c retained substantial binding toward PBP2a with 61.5% shorter sequence than the original Aptamer 63. Therefore, further studies are required by employing molecular docking and extended molecular dynamics simulations to further optimize binding performance.