Gentianine is one of the compounds found in the plant Swertiya chirayita that is known for its antimalarial activity. However, its exact molecular mechanism of action is yet to be understood. In our present study, we applied several computational approaches to filter out and determine possible targets of gentianine in Plasmodium falciparum 3D7. Protein-protein networks formed the basis of one of our strategies along with orthologous protein analysis to establish essentiality. Out of 6 essential proteins from unique pathways, haloacid dehalogenase like-hydrolase (PfHAD1), phosphoenolpyruvate carboxykinase (PfPEPCK) and fumarate hydratase (PfFH) were screened as drug targets through this approach. Through our other strategy we established the predicted IC50 (PIC50) value of gentianine with a set of molecular descriptors from 123 Pathogen Box anti-malarial compounds. Afterwards through 2D structural similarity, L-lactate dehydrogenase (PfLDH) was established as another possible target. In our work, we performed in silico docking and analysed the binding of gentianine to the proteins. All of the proteins were reported with favourable binding results and were considered for complex molecular dynamics simulation approach. Our research clears up the molecular mechanism of antimalarial activity of gentianine to some extent paving way for experimental validation of the same in future.

龙胆碱是在Swertiya chirayita植物中发现的化合物之一，以其抗疟活性而闻名。然而，其确切的分子作用机理尚待了解。在我们目前的研究中，我们应用了几种计算方法来筛选和确定恶性疟原虫3D7中的龙胆碱目标。蛋白质-蛋白质网络与直系同源蛋白质分析一起建立必要性，是我们策略之一。在来自独特途径的6种必需蛋白质中，卤酸脱卤素酶类似水解酶（Pf HAD1），磷酸烯醇丙酮酸羧化激酶（Pf PEPCK）和富马酸盐水合酶（Pf通过这种方法将FH）筛选为药物靶标。通过我们的其他策略，我们利用123种病原体抗疟化合物的一组分子描述符，建立了龙胆碱的预测IC50（PIC50）值。之后，通过2D结构相似性，L-乳酸脱氢酶（Pf LDH）被确立为另一个可能的靶标。在我们的工作中，我们进行了计算机对接，并分析了龙胆碱与蛋白质的结合。据报道所有蛋白质均具有良好的结合结果，并被考虑用于复杂的分子动力学模拟方法。我们的研究为龙胆碱的抗疟活性清除了分子机制，为今后的实验验证铺平了道路。