甘氨酸羟甲基转移酶是嘌呤、胸腺嘧啶和L-丝氨酸生物合成中的重要参与者，并被标记为治疗癌症、病毒和寄生虫的潜在靶点。然而，作为一种抗菌药物可靶标的酶尚未得到广泛研究。本文使用不同的计算化学和生物物理学技术，对肠球菌粪肠球菌甘氨酸羟甲基转移酶进行了潜在计算预测抑制分子的鉴定工作。通过针对该酶的基于结构的虚拟筛选过程，报道了两种主要化合物：Top-1_BDC_21204033和Top-2_BDC_20700155作为最佳结合分子。Top-1_BDC_21204033和Top-2_BDC_20700155的结合能值分别为-9.3和-8.9kcal/mol。对照分子的结合能得分为-6.55kcal/mol。Top-1-BDC_21204033、Top-2-BDC_20700155和对照分子的平均RMSD分别为3.7Å（最大值5.03Å）、1.7Å（最大值3.05Å）和3.84Å（最大值6.7Å）。在模拟时间内，尽管化合物/对照分子存在少量小跳跃，但其分子间结合构象和相互作用保持稳定，导致某些帧的RMSD较高。MM/GBSA和MM/PBSA位于Top-2-BDC_20700155复合物的结合自由能分别为-79.52和-82.63kcal/mol。相对于对照分子，该复合物较为稳定。此外，领头分子和对照分子表现出良好的药物样性和药代动力学特性。领头分子无毒性和无突变性。简言之，这些化合物在与甘氨酸羟甲基转移酶结合方面具有潜力，需要接受实验研究的检验。由Ramaswamy H. Sarma转载。

Serine hydroxymethyltransferase enzyme is a significant player in purine, thymidylate, and L-serine biosynthesis and has been tagged as a potential target for cancer, viruses, and parasites. However, this enzyme as an anti-bacterial druggable target has not been explored much. Herein, in this work, different computational chemistry and biophysics techniques were applied to identify potential computational predicted inhibitory molecules against Enterococcus faecium serine hydroxymethyltransferase enzyme. By structure based virtual screening process of ASINEX antibacterial library against the enzyme two main compounds: Top-1_BDC_21204033 and Top-2_BDC_20700155 were reported as best binding molecules. The Top-1_BDC_21204033 and Top-2_BDC_20700155 binding energy value is -9.3 and -8.9 kcal/mol, respectively. The control molecule binding energy score is -6.55 kcal/mol. The mean RMSD of Top-1-BDC_21204033, Top-2-BDC_20700155 and control is 3.7 Å (maximum 5.03 Å), 1.7 Å (maximum 3.05 Å), and 3.84 Å (maximum of 6.7 Å), respectively. During the simulation time, the intermolecular docked conformation and interactions were seen stable despite of few small jumps by the compounds/control, responsible for high RMSD in some frames. The MM/GBSA and MM/PBSA binding free energy of lead Top-2-BDC_20700155 complex is -79.52 and -82.63 kcal/mol, respectively. This complex was seen as the most stable compared to the control. Furthermore, the lead molecules and control showed good druglikeness and pharmacokinetics profile. The lead molecules were non-toxic and non-mutagenic. In short, the compounds are promising in terms of binding to the serine hydroxymethyltransferase enzyme and need to be subjected to experimental studies.Communicated by Ramaswamy H. Sarma.