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Abstract：
Trypsin inhibitors from tamarind seed have been studied in vitro and in preclinical studies for the treatment of obesity, its complications and associated comorbidities. It is still necessary to fully understand the structure and behaviour of these molecules. We purifed this inhibitor, sequenced de novo by MALDI-TOF/TOF, performed its homology modelling, and assessed the interaction with the trypsin enzyme through molecular dynamics (MD) simulation under physiological conditions. We identified additional 75 amino acid residues, reaching approximately 72% of total coverage. The four best conformations of the best homology modelling were submitted to the MD. The conformation n°287 was selected considering the RMSD analysis and interaction energy (-301.0128 kcal.mol-1). Residues Ile (54), Pro (57), Arg (59), Arg (63), and Glu (78) of pTTI presented the highest interactions with trypsin, and arginine residues were mainly involved in its binding mechanism. The results favour bioprospecting of this protein for pharmaceutical health applications.
摘要：
已经在体外和临床前研究中研究了罗望子种子的胰蛋白酶抑制剂，用于治疗肥胖症，其并发症和相关的合并症。仍然有必要充分了解这些分子的结构和行为。我们净化了这种抑制剂，由MALDI-TOF/TOF从头排序，进行了同源性建模，并通过分子动力学（MD）模拟评估了在生理条件下与胰蛋白酶酶的相互作用。我们鉴定了另外75个氨基酸残基，达到总覆盖率的大约72%。将最佳同源性建模的四个最佳构象提交给MD。考虑RMSD分析和相互作用能(-301.0128kcal)选择构象n°287。mol-1)。剩余物Ile(54)，Pro(57),Arg(59),Arg(63),pTTI的Glu(78)与胰蛋白酶的相互作用最高，精氨酸残基主要参与其结合机制。结果有利于该蛋白质用于药物健康应用的生物勘探。
