Staphylococcus aureus is resistant to β-lactam antibiotics and causes several skin diseases to life-threatening diseases. FmtA is found to be one of the main factors involved in methicillin resistance in S. aureus. FmtA exhibits an esterase activity that removes the D-Ala from teichoic acid. Teichoic acids played a significant role in cell wall synthesis, cell division, colonization, biofilm formation, virulence, antibiotic resistance, and pathogenesis. The virtual screening of drug molecules against the crystal structure of FmtA was performed and the binding affinities of top three molecules (ofloxacin, roflumilast, and furazolidone) were predicted using molecular docking. The presence of positive potential and electron affinity regions in screened drug molecules by DFT analysis illustrated that these molecules are reactive in nature. The protein–ligand complexes were subjected to molecular dynamics simulation. Molecular dynamics analysis such as RMSD, RMSF, Rg, SASA, PCA, and FEL results suggested that FmtA-drug(s) complexes are stable. MM-GBSA binding affinity and QM/MM results (ΔG, ΔH, and ΔS) revealed that active site residues (Ser127, Lys130, Tyr211, Asp213, and Asn343) of FmtA played an essential for the binding of the drug(s) to form a lower energy stable protein–ligand complexes. FmtA^Δ42 was purified using cation exchange and gel filtration chromatography. Fluorescence spectroscopy and circular dichroism results showed that interactions of drugs with FmtA^Δ42 affect the tertiary structure and increase the thermostability of the protein. The screened molecules need to be tested and could be further modified to develop the antimicrobial compounds against S. aureus.

金黄色葡萄球菌对β-内酰胺类抗生素具有抗药性，可引起多种皮肤病甚至危及生命的疾病。发现 FmtA 是金黄色葡萄球菌甲氧西林耐药的主要因素之一. FmtA 表现出从磷壁酸中去除 D-Ala 的酯酶活性。磷壁酸在细胞壁合成、细胞分裂、定植、生物膜形成、毒力、抗生素抗性和发病机制中发挥了重要作用。进行了针对 FmtA 晶体结构的药物分子的虚拟筛选，并使用分子对接预测了前三种分子（氧氟沙星、罗氟司特和呋喃唑酮）的结合亲和力。通过 DFT 分析筛选出的药物分子中存在正电位和电子亲和区表明这些分子本质上是反应性的。蛋白质-配体复合物进行分子动力学模拟。分子动力学分析如 RMSD、RMSF、Rg、SASA、PCA 和 FEL 结果表明 FmtA-药物复合物是稳定的。MM-GBSA 结合亲和力和 QM/MM 结果（ΔG、ΔH 和 ΔS）表明 FmtA 的活性位点残基（Ser127、Lys130、Tyr211、Asp213 和 Asn343）对于药物与形成低能量稳定的蛋白质-配体复合物。FmtA使用阳离子交换和凝胶过滤色谱纯化^Δ42。荧光光谱和圆二色性结果表明，药物与 FmtA ^{Δ42 的相互作用}会影响蛋白质的三级结构并增加蛋白质的热稳定性。筛选出的分子需要进行测试，并可以进一步修改以开发抗金黄色葡萄球菌的抗菌化合物。