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None of the reboot sisters can say as much, as Mel was forced to give up her job as a TA due to rewriting history and getting a job as a bartender, then being forced to give that up in S2 and essentially being in hiding for the whole season before somehow in S3 getting yet another job as a professor at a uni… which is promptly forgotten about over the course of the show. That in itself is a political statement, especially for the time period. Prue, Piper, and Phoebe all eventually had high-paying jobs and successful careers, with Piper owning her own nightclub and at the end of the series finally opening up her own restaurant. However, for the last 25 years, theoretical developments, better computational algorithms, faster computing resources, and improved visualization tools enabled the routine use of computational methods to model and visualize protein-ligand (PL) interactions, calculate binding free energy to different degrees of accuracy, and in silico screen chemical libraries using ligand-based and structure-based approaches. In spite of multiple efforts to improve its performance, drug discovery remains a costly and time consuming technique ( Phatak et al., 2009). For many years, both the identification and optimization of novel drug lead compounds were accomplished within the drug discovery process by the experimental high-throughput screening of large chemical libraries. The cost to bring a new drug to the market could be as high as 2.6 billion US dollars, and can take up to 15 years ( DiMasi et al., 2016). It is thus urgently needed to develop and validate novel quantum mechanical-based scoring functions for high-throughput docking toward more accurate methods for the identification and optimization of modulators of pharmaceutically relevant targets. It is acknowledged that developments in quantum mechanics theory, algorithms and computer hardware throughout the upcoming years will allow semi-empirical (or low-cost) quantum mechanical methods to slowly replace force-field calculations. Outstanding results were obtained, with our QM scoring function displaying much higher enrichment (screening power) than a traditional docking method. In this work, we introduce a QM-based docking scoring function for high-throughput docking and evaluate it on 10 protein systems belonging to diverse protein families, and with different binding site characteristics. However, to better characterize protein-ligand interactions, the use of a more accurate quantum mechanical (QM) description would be necessary. Most docking programs are rooted in classical molecular mechanics. While there has been an impressive methodological improvement in docking accuracy, docking scoring still remains an open challenge. Today high-throughput docking is one of the most commonly used computational tools in drug lead discovery. 3Austral Institute for Applied Artificial Intelligence, Universidad Austral, Pilar, Argentina.2Facultad de Ciencias Biomédicas and Facultad de Ingeniería, Universidad Austral, Pilar, Argentina.1Computational Drug Design and Biomedical Informatics Laboratory, Translational Medicine Research Institute (IIMT), CONICET-Universidad Austral, Pilar, Argentina. However, he announced in his social network site that he would be teaming up with ace actor – director V. 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Soon afterwards, the rivals come and start killing everyone. During the marriage the Inspector tells his father that the enmity is rekindling because his son is taking revenge on the rivals. Then they decide to marry Vijay with Sindhu because they both are in love with each other. He starts taking revenge on the Manasa's family without revealing his identity. When Vijay goes there, he falls in love with Sindhu ( Varalaxmi Sarathkumar). But his mother Lavanya ( Ramya Krishna) didn't want to stay there, so she left him. Ravichandran) wanted to change the people of his village. It is then revealed that he was born to their rival's family. In his conservative and ancestral village, Vijay changes everyone's viewpoint and makes them more lovable.Įventually Manasa expresses her love for him, but Vijay hesitates. He then goes back to India and influences Manasa's brother to a large extent. 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If a king left behind multiple sons when he died, and the eldest had no children when he succeeded his father as king, the next oldest son would become Prince of Dragonstone, as his brother's legal heir. In practice, if the heir apparent had not yet reached the age of legal majority, a regent (usually a blood relative) would administer Dragonstone in the interim - but the under-aged heir would still nominally be Prince of Dragonstone. While kings of the Targaryen dynasty ruled from the Iron Throne in King's Landing, the heir to the throne would traditionally rule over the ancestral Targaryen lands: the volcanic island of Dragonstone, located on the far side of Blackwater Bay from King's Landing itself.ĭragonstone was usually ruled by the crown prince. The title was created after Aegon I Targaryen unified the Seven Kingdoms in the War of Conquest. Prince of Dragonstone is a title traditionally given to the heir apparent to the ruling monarch of the Seven Kingdoms. 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