Setlur Anagha S, Niranjan Vidya, Karunakaran Chandrashekar, Sambanni Varun S, Sharma Dileep, Pai Karthik
Department of Biotechnology, RV College of Engineering affiliated to Visvesvaraya Technological University (VTU), Belagavi, 590018, India.
Department of Computer Science and Engineering, RV College of Engineering affiliated to Visvesvaraya Technological University (VTU), Belagavi, 590018, India.
Mol Biotechnol. 2025 Jul;67(7):2798-2816. doi: 10.1007/s12033-024-01241-3. Epub 2024 Jul 24.
A comprehensive examination of Aedes aegypti's proteome to detect key proteins that can be targeted with small molecules can disrupt blood feeding and disease transmission. However, research currently only focuses on finding repellent-like compounds, limiting studies on identifying unexplored proteins in its proteome. High-throughput analysis generates vast amounts of data, raising concerns about accessibility and usability. Establishing a dedicated database is a solution, centralizing information on identified proteins, functions, and modeled structures for easy access and research. This study focuses on scrutinizing key proteins in A. aegypti, modeling their structures using RaptorX standalone tool, identification of druggable binding sites using BiteNet, validating the models via Ramachandran plot studies and refining them via 50-ns molecular dynamic simulations using Schrodinger Maestro. By analyzing ~ 18 k proteins in the proteome of A. aegypti in our previous studies, all proteins involved in the light and dark circadian rhythm of the mosquito, inclusive of proteins in blood feeding, metabolism, etc. were chosen for the current study. The outcome is UAAPRD, a unique repository housing information on hundreds of previously unmodeled and un-simulated mosquito proteins. This robust MYSQL database ( https://uaaprd.onrender.com/user ) houses data on 309 modeled & simulated proteins of A. aegypti. It allows users to obtain protein data, view evolutionary analysis data of the protein categories, visualize proteins of interest, and send request to screen against the pharmacophore models present in UAAPRD against ligand of interest. This study offers crucial insights for developing targeted studies, which will ultimately contribute to more effective vector control strategies.
对埃及伊蚊蛋白质组进行全面检测，以发现可被小分子靶向的关键蛋白质，这可能会干扰其血液摄取和疾病传播。然而，目前的研究仅集中在寻找类似驱避剂的化合物，限制了对其蛋白质组中未探索蛋白质的鉴定研究。高通量分析产生了大量数据，引发了对数据可访问性和可用性的担忧。建立一个专用数据库是一种解决方案，它将已鉴定蛋白质、功能和建模结构的信息集中起来，便于访问和研究。本研究着重仔细研究埃及伊蚊中的关键蛋白质，使用RaptorX独立工具对其结构进行建模，使用BiteNet识别可成药结合位点，通过拉氏图研究验证模型，并使用Schrodinger Maestro通过50纳秒的分子动力学模拟对其进行优化。通过在我们之前的研究中分析埃及伊蚊蛋白质组中的约18k种蛋白质，选择了所有参与蚊子昼夜节律的蛋白质，包括血液摄取、代谢等过程中的蛋白质用于当前研究。结果是UAAPRD，这是一个独特的储存库，包含了数百种以前未建模和未模拟的蚊子蛋白质的信息。这个强大的MYSQL数据库（https://uaaprd.onrender.com/user）存储了309种埃及伊蚊建模和模拟蛋白质的数据。它允许用户获取蛋白质数据，查看蛋白质类别的进化分析数据，可视化感兴趣的蛋白质，并发送请求以根据UAAPRD中存在的药效团模型针对感兴趣的配体进行筛选。这项研究为开展针对性研究提供了关键见解，最终将有助于制定更有效的病媒控制策略。
