Joseph Sahayarayan Jesudass, Soundar Rajan Kulanthaivel, Nachiappan Mutharasappan, Prabhu Dhamodharan, Guru Raj Rao Ravi, Jeyakanthan Jeyaraman, Hossam Mahmoud Ahmed, Mohammed Osama B, Morgan Abubaker M A
Department of Bioinformatics, Alagappa University, Karaikudi, Tamil Nadu 630 003, India.
Department Zoology, College of Science, King Saud University, P.O Box 2455, Riyadh 11451, Saudi Arabia.
Saudi J Biol Sci. 2020 Dec;27(12):3327-3333. doi: 10.1016/j.sjbs.2020.10.019. Epub 2020 Oct 16.
Malaria caused by genus a parasite which is the main health issue for humans and about half of the population were suffered. An every year, approximately 1.2-2.7 million people died due to malaria globally. Therefore to prevent the spreading of malaria from the glob novel active drugs with specific activities are necessary. The present study aimed to identify novel drug molecule together with the bioinformatic tools for the development of active malarial drugs. As the search for latest anti malarial compound was developed, this work determined six active blends from various drug databases which possess drug-like characteristics and presents a significant anti malarial actions in level. Compound ID 300238, 889, 76569, 87324, 45678, and Z185397112are a few of the ligands were got from the Toss lab, Maybridge, Cambridge, Life chem, Bitter, and Examine drug databases and docked against hexokinase 1 protein (PDB: 1CZA) with high throughput practical screening (HTVS) using Glide v6.6. Amid the 6 compounds, compound no: 300238 from Toss lab has the greatest docking score of -9.889 kcal/mol targeting 1CZA protein. The active sites of Hexokinase I of protein were determine by using superimposition of the destination and template structure showed similar structural folds and active sites which were decidedly conserved. The quality of hexokinase I protein was considered to be sterically stable where the protein was prepared by utilizing the software protein preparation execute in the Schrodinger suite. Prepared proteins were evaluated using SAVES and the studies of molecular dynamics of the hexokinase, and the GROMACS were performed for protein-ligand complex. The low HOMO-LUMO energy gaps of the compound verified the greater stability of the molecule. Here, the tested drug candidates have good absorption, distribution, metabolism, and excretion (ADME) properties which were established by using QikProp, version 3.4 of Schrodinger.
疟原虫属引起的疟疾是人类主要的健康问题，约一半人口受其影响。全球每年约有120万至270万人死于疟疾。因此，为防止疟疾在全球传播，需要研发具有特定活性的新型活性药物。本研究旨在利用生物信息学工具鉴定新型药物分子，以开发活性抗疟药物。随着对最新抗疟化合物的研究不断深入，本研究从各种药物数据库中确定了六种具有类药物特性且具有显著抗疟活性的活性混合物。化合物ID 300238、889、76569、87324、45678和Z185397112是从Toss实验室、剑桥的Maybridge、Life chem、Bitter和Examine药物数据库中获得的一些配体，并使用Glide v6.6通过高通量虚拟筛选（HTVS）与己糖激酶1蛋白（PDB：1CZA）进行对接。在这6种化合物中，来自Toss实验室的化合物编号300238对1CZA蛋白的对接分数最高，为-9.889 kcal/mol。通过目标结构与模板结构的叠加确定了蛋白己糖激酶I的活性位点，结果显示它们具有相似的结构折叠和活性位点，且这些位点具有明显的保守性。利用Schrodinger套件中的蛋白质制备软件制备的己糖激酶I蛋白在空间上被认为是稳定的。使用SAVES对制备的蛋白质进行评估，并对己糖激酶进行分子动力学研究，同时使用GROMACS对蛋白质-配体复合物进行研究。化合物较低的最高占据分子轨道-最低未占据分子轨道（HOMO-LUMO）能隙验证了分子的更高稳定性。在此，通过使用Schrodinger的QikProp 3.4版本确定了受试候选药物具有良好的吸收、分布、代谢和排泄（ADME）特性。
