分类： 化学 >> 物理化学 提交时间： 2017-11-05 合作期刊: 《结构化学》
摘要： The adsorption process and hydrogenation mechanisms of 2-methylthiophene on the Pt(111) surface have been elucidated using density functional theory (DFT). The optimal adsorption sites of reactants, intermediates, and products as well as the activation energy and reaction energy of each elementary reactions were investigated. The results turned out that the 2-methylthiophene tilt to the Pt(111) catalyst with the C1–C2 double bond at the top site was the most stable. During the hydrogenation process, the heat of reaction almost located at the negative side, so dropping the temperature is good for the occurrence of hydrogenation process. The hydrogenation steps of mechanism take place along C2→C3→C1→C4→S→C1 to generate the product of pentane-2-thiol, in which the first step with the highest energy barrier is the rate-determining step.
分类： 药物科学 >> 药物设计 提交时间： 2024-02-20
Jin Liu
Yike Gui
Jingxin Rao
Jingjing Sun
Gang Wang
Qun Ren
Ning Qu
Buying Niu
Zhiyi Chen
Xia Sheng
Yitian Wang
Mingyue Zheng
Xutong Li
摘要： Ensuring drug safety in the early stages of drug development is crucial to avoid costly failures in subsequent phases. However, the economic burden associated with detecting drug off-targets and potential side effects through in vitro safety screening and animal testing is substantial. Drug off-target interactions, along with the adverse drug reactions they induce, are significant factors affecting drug safety. To assess the liability of candidate drugs, we developed an artificial intelligence model for the precise prediction of compound off-target interactions, leveraging multi-task graph neural networks. The outcomes of off-target predictions can serve as representations for compounds, enabling the differentiation of drugs under various ATC codes and the classification of compound toxicity. Furthermore, the predicted off-target profiles are employed in ADR enrichment analysis, facilitating the inference of potential ADRs for a drug. Using the withdrawn drug Pergolide as an example, we elucidate the mechanisms underlying ADRs at the target level, contributing to the exploration of the potential clinical relevance of newly predicted off-target interactions. Overall, our work facilitates the early assessment of compound safety/toxicity based on off-target identification, deduces potential ADRs of drugs, and ultimately promotes the secure development of drugs.
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