Rangisetty Pranaya Thara, Kilaparthi Asrita, Akula Sreevidya, Bhardwaj Mahima, Singh Sachidanand
Department of Biotechnology, Vignan's Foundation for Science, Technology and Research, Guntur, Andhra Pradesh, India.
Department of Biotechnology, Sankalchand Patel University, Visnagar, Gujarat, India.
Int J Health Sci (Qassim). 2023 Jan-Feb;17(1):12-17.
The major purpose of the present study was to predict the structure of Radical s-adenosyl-L-methionine Domain 2 (RSAD2), the most targeted protein of the Zika virus using comparative modeling, to validate the models that were generated and molecular dynamics (MD) simulations were performed.
The secondary structure of RSAD2 was estimated using the Garnier-Osguthorpe-Robson, Self-Optimized Prediction method with Alignment, and Position-Specific Iterative-Blast based secondary structure prediction algorithms. The best of them were preferred based on their DOPE score, then three-dimensional structure identification using SWISS-MODEL and the Protein Homology/Analogy Recognition Engine (Phyre2) server. SAVES 6.0 was used to validate the models, and the preferred model was then energetically stabilized. The model with least energy minimization was used for MD simulations using iMODS.
The model predicted using SWISS-MODEL was determined as the best among the predicted models. In the Ramachandran plot, there were 238 residues (90.8%) in favored regions, 23 residues (8.8%) in allowed regions, and 1 residue (0.4%) in generously allowed regions. Energy minimization was calculated using Swiss PDB viewer, reporting the SWISS-MODEL with the lowest energy (E = -18439.475 KJ/mol) and it represented a stable structure conformation at three-dimensional level when analyzed by MD simulations.
A large amount of sequence and structural data is now available, for tertiary protein structure prediction, hence implying a computational approach in all the aspects becomes an opportunistic strategy. The best three-dimensional structure of RSAD2 was built and was confirmed with energy minimization, secondary structure validation and torsional angles stabilization. This modeled protein is predicted to play a role in the development of drugs against Zika virus infection.
本研究的主要目的是通过比较建模预测寨卡病毒最具靶向性的蛋白质——自由基S-腺苷-L-甲硫氨酸结构域2（RSAD2）的结构，对生成的模型进行验证并进行分子动力学（MD）模拟。
使用 Garnier-Osguthorpe-Robson、带比对的自优化预测方法以及基于位置特异性迭代比对的二级结构预测算法来估计RSAD2的二级结构。根据它们的DOPE分数选择最佳算法，然后使用SWISS-MODEL和蛋白质同源性/类比识别引擎（Phyre2）服务器进行三维结构识别。使用SAVES 6.0验证模型，然后对优选模型进行能量稳定化处理。使用iMODS对能量最小化程度最低的模型进行MD模拟。
使用SWISS-MODEL预测的模型被确定为预测模型中的最佳模型。在拉氏图中，有利区域有238个残基（90.8%），允许区域有23个残基（8.8%），宽松允许区域有1个残基（0.4%）。使用瑞士PDB查看器计算能量最小化，结果显示SWISS-MODEL的能量最低（E = -18439.475 KJ/mol），通过MD模拟分析表明其在三维水平上代表一种稳定的结构构象。
现在有大量的序列和结构数据可用于三级蛋白质结构预测，因此在各个方面采用计算方法成为一种机会主义策略。构建了RSAD2的最佳三维结构，并通过能量最小化、二级结构验证和扭转角稳定化得到了证实。该建模蛋白质预计在抗寨卡病毒感染药物的开发中发挥作用。
