In-silico and in-vitro study of novel antimicrobial peptide AM1 from Aegle marmelos against drug-resistant Staphylococcus aureus

Antimicrobial peptides have garnered increasing attention as potential alternatives due to their broad-spectrum antimicrobial activity and low propensity for developing resistance. This is for the first time; proteome sequences of Aegle marmelos were subjected to in-silico digestion and AMP prediction were performed using DBAASP server. After screening the peptides on the basis of different physiochemical property, peptide sequence GKEAATKAIKEWGQPKSKITH (AM1) shows the maximum binding affinity with 10.2 Kcal/mol in comparison with the standard drug (Trimethoprim) with 7.4 kcal/mol and 6.8 Kcal/mol for DHFR and SaTrmK enzyme respectively. Molecular dynamics simulation performed for 300ns, it has been found that peptide was able to stabilize the protein more effectively, analysed by RMSD, RMSF, and other statistical analysis. Free binding energy for DHFR and SaTrmK interaction from MMPBSA analysis with peptide was found to be -47.69 and 44.32 Kcal/mol and for Trimethoprim to be -13.85 Kcal/mol and 11.67 Kcal/mol respectively. Further in-vitro study was performed against Methicillin Susceptible Staphylococcus aureus (MSSA), Methicillin Resistant Staphylococcus aureus (MRSA), Multi-Drug Resistant Staphylococcus aureus (MDR-SA) strain, where MIC values found to be 2, 4, and 8.5 g/ml lesser in comparison to trimethoprim which has higher MIC values 2.5, 5, and 9.5 g/ml respectively. Thus, our study provides the insight for the further in-vivo study of the peptides against multi-drug resistant S. aureus .Supplementary Information The online version contains supplementary material available at 10.1038/s41598-024-76553-0.