Health Information Technology Department, The Applied College, King Abdulaziz University, Jeddah, Saudi Arabia.
Centre for Artificial Intelligence in Precision Medicines, King Abdulaziz University, Jeddah, Saudi Arabia.
J Biomol Struct Dyn. 2024 Aug;42(13):6799-6812. doi: 10.1080/07391102.2023.2238088. Epub 2023 Jul 22.
is a Gram-negative bacterial pathogen that causes bacteremia, urinary tract infections, intra-abdominal infections, chorioamnionitis, neonatal sepsis, and newborn meningitis. To control this bacterial pathogen a total of 3565 putative proteins targets in were screened using comparative subtractive analysis of biochemical pathways annotated by the KEGG that did not share any similarities with human proteins. One of the targets, D-alanyl-D-alanine carboxypeptidase DacB [] was observed to be implicated in the majority of cell wall synthesis pathways, leading to its selection as a novel pharmacological target. The drug that interacted optimally with the identified target was observed to be Cefoperazone (DB01329) with the estimated free energy of binding -8.9 Kcal/mol. During molecular dynamics simulations; it was observed that DB01328-2exb and DB01329-2exb complexes showed similar values as the control FMX-2exb complex near 0.2 nm with better stability. Furthermore, MMPBSA total free energy calculation showed better binding energy than the control complex for DB01329-2exb interaction i.e. -31.50 (±0.93) kcal/mol. Our presented research suggested that D-alanyl-D-alanine carboxypeptidase DacB could be a therapeutic target and cefoperazone could be a promising ligand to inhibit the D-alanyl-D-alanine carboxypeptidase DacB protein of . To identify prospective therapeutic and vaccine targets in , this is the first computational and subtractive genomics investigation of various metabolic pathways exploring other therapeutic targets of experimental validation of the identified target D-alanyl-D-alanine carboxypeptidase and the design of its inhibitors is suggested to figure out the best dose, the drug's effectiveness, and its toxicity.Communicated by Ramaswamy H. Sarma.
是一种革兰氏阴性细菌病原体，可导致菌血症、尿路感染、腹腔内感染、绒毛膜羊膜炎、新生儿败血症和新生儿脑膜炎。为了控制这种细菌病原体，共筛选了 3565 个潜在的蛋白质靶点，这些靶点是通过对 KEGG 注释的生化途径进行比较性消减分析得到的，与人类蛋白质没有任何相似之处。其中一个靶点 D-丙氨酰-D-丙氨酸羧肽酶 DacB[]被观察到与大多数细胞壁合成途径有关，因此被选为新的药理靶点。与鉴定的靶点最佳相互作用的药物被观察到是头孢哌酮（DB01329），结合自由能为-8.9 Kcal/mol。在分子动力学模拟中；观察到 DB01328-2exb 和 DB01329-2exb 复合物在接近 0.2nm 处与对照 FMX-2exb 复合物具有相似的值，稳定性更好。此外，MMPBSA 总自由能计算显示，与对照复合物相比，DB01329-2exb 相互作用的结合能更好，即-31.50（±0.93）kcal/mol。我们的研究表明，D-丙氨酰-D-丙氨酸羧肽酶 DacB 可能是一个治疗靶点，头孢哌酮可能是一个有前途的配体，可以抑制 D-丙氨酰-D-丙氨酸羧肽酶 DacB 蛋白。为了确定 的潜在治疗和疫苗靶点，这是对各种代谢途径进行计算和消减基因组学研究的首次尝试，以探索 的其他治疗靶点，实验验证鉴定的靶标 D-丙氨酰-D-丙氨酸羧肽酶，并设计其抑制剂，以确定最佳剂量、药物的有效性及其毒性。由 Ramaswamy H. Sarma 传达。
