Further Insights in the Binding Mode of Selective Inhibitors to Human PDE4D Enzyme Combining Docking and Molecular Dynamics

DUrsi Pasqualina; Guariento Sara; Trombetti Gabriele; Orro Alessandro; Cichero Elena; Milanesi Luciano; Fossa Paola; Bruno Olga

摘要

Abstract >Alzheimer′s disease has recently emerged as a possible field of application for PDE4D inhibitors (PDE4DIs). The great structure similarity among the various PDE4 isoforms and, furthermore, the lack of the full length crystal structure of the enzyme, impaired the rational design of new selective PDE4DIs. In this paper, with the aim of exploring new insights into the PDE4D binding, we tackled the problem by performing a computational study based on docking simulations combined with molecular dynamics (D‐MD). Our work uniquely identified the binding mode and the key residues involved in the interaction with a number of in‐house catechol iminoether derivatives, acting as PDE4DIs. Moreover, the new binding mode was tested using a series of analogues previously reported by us and it was used to confirm their key structural features to allow PDE4D inhibition. The binding model disclosed within the current computational study may prove to be useful to further advance the design and synthesis of novel, more potent and selective, PDE4D inhibitors. </abstract> </span> <span class="z_kbtn z_kbtnclass hoverxs" style="display: none;">展开▼</span> </div> <div class="translation abstracttxt"> <span class="zhankaihshouqi fivelineshidden" id="abstract"> <span>机译：</span><abstract xmlns =“http://www.wiley.com/namespaces/wiley”type =“main”xml：lang =“en”> <title type =“main”>抽象</ title> > alzheimer'最近患有PDE4D抑制剂（PDE4DIS）的可能施用领域。各种PDE4同种型之间的结构相似性很大，而且还缺乏酶的全长晶体结构，损害了新选择性PDE4DIS的合理设计。在本文中，目的是通过对基于对接模拟的基于分子动力学（D-MD）的计算研究进行计算研究，探讨了新的洞察力。我们的工作唯一地鉴定了与许多内部儿茶酚亚替酯衍生物相互作用的结合模式和关键残留物，其作用为PDE4DIS。此外，使用先前由我们报告的一系列类似物测试了新的结合模式，用来确认其关键结构特征以允许PDE4D抑制。当前计算研究中公开的结合模型可以证明是进一步推进新颖，更有效和选择性的PDE4D抑制剂的设计和合成的有用。</ p> </摘要> </span> <span class="z_kbtn z_kbtnclass hoverxs" style="display: none;">展开▼</span> </div> </div> <div class="record"> <h2 class="all_title" id="enpatent33" >著录项</h2> <ul> <li> <span class="lefttit">来源</span> <div style="width: 86%;vertical-align: text-top;display: inline-block;"> <a href='/journal-foreign-25225/'>《Molecular informatics》</a> <b style="margin: 0 2px;">|</b><span>2016年第9期</span><b style="margin: 0 2px;">|</b><span>共13页</span> </div> </li> <li> <div class="author"> <span class="lefttit">作者</span> <p id="fAuthorthree" class="threelineshidden zhankaihshouqi"> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=DUrsi Pasqualina&option=202" target="_blank" rel="nofollow">DUrsi Pasqualina;</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Guariento Sara&option=202" target="_blank" rel="nofollow">Guariento Sara;</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Trombetti Gabriele&option=202" target="_blank" rel="nofollow">Trombetti Gabriele;</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Orro Alessandro&option=202" target="_blank" rel="nofollow">Orro Alessandro;</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Cichero Elena&option=202" target="_blank" rel="nofollow">Cichero Elena;</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Milanesi Luciano&option=202" target="_blank" rel="nofollow">Milanesi Luciano;</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Fossa Paola&option=202" target="_blank" rel="nofollow">Fossa Paola;</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Bruno Olga&option=202" target="_blank" rel="nofollow">Bruno Olga;</a> </p> <span class="z_kbtnclass z_kbtnclassall hoverxs" id="zkzz" style="display: none;">展开▼</span> </div> </li> <li> <div style="display: flex;"> <span class="lefttit">作者单位</span> <div style="position: relative;margin-left: 3px;max-width: 639px;"> <div class="threelineshidden zhankaihshouqi" id="fOrgthree"> <p>Institute for Biomedical Technologies e National Research Council (ITB-CNR)Via Fratelli Cervi 93;</p> <p>Department of Pharmacy Section of Medicinal Chemistry School of Medical and Pharmaceutical;</p> <p>Institute for Biomedical Technologies e National Research Council (ITB-CNR)Via Fratelli Cervi 93;</p> <p>Institute for Biomedical Technologies e National Research Council (ITB-CNR)Via Fratelli Cervi 93;</p> <p>Department of Pharmacy Section of Medicinal Chemistry School of Medical and Pharmaceutical;</p> <p>Institute for Biomedical Technologies e National Research Council (ITB-CNR)Via Fratelli Cervi 93;</p> <p>Department of Pharmacy Section of Medicinal Chemistry School of Medical and Pharmaceutical;</p> <p>Department of Pharmacy Section of Medicinal Chemistry School of Medical and Pharmaceutical;</p> </div> <span class="z_kbtnclass z_kbtnclassall hoverxs" id="zhdw" style="display: none;">展开▼</span> </div> </div> </li> <li > <span class="lefttit">收录信息</span> <span style="width: 86%;vertical-align: text-top;display: inline-block;"></span> </li> <li> <span class="lefttit">原文格式</span> <span>PDF</span> </li> <li> <span class="lefttit">正文语种</span> <span>eng</span> </li> <li> <span class="lefttit">中图分类</span> <span><a href="https://www.zhangqiaokeyan.com/clc/173.html" title="普通生物学">普通生物学;</a></span> </li> <li class="antistop"> <span class="lefttit">关键词</span> <p style="width: 86%;vertical-align: text-top;"> <a style="color: #3E7FEB;" href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Phosphodiesterases&option=203" rel="nofollow">Phosphodiesterases;</a> <a style="color: #3E7FEB;" href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=PDE4&option=203" rel="nofollow">PDE4;</a> <a style="color: #3E7FEB;" href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=PDE4D selective inhibitors&option=203" rel="nofollow">PDE4D selective inhibitors;</a> <a style="color: #3E7FEB;" href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=docking&option=203" rel="nofollow">docking;</a> <a style="color: #3E7FEB;" href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=molecular dynamics&option=203" rel="nofollow">molecular dynamics;</a> </p> <div class="translation"> 机译：磷酸二酯酶;PDE4;PDE4D选择性抑制剂;对接;分子动力学; </div> </li> </ul> </div> </div> <div class="literature cardcommon" id="literaturereference" style="display:none"> <div class="similarity "> <h3 class="all_title" id="enpatent111">引文网络</h3> <div class="referencetab clearfix"> <ul id="referencedaohang"> <li dataid="referenceul">参考文献</li> <li dataid="citationul">引证文献</li> <li dataid="commonreferenceul">共引文献</li> <li dataid="commoncitationul">同被引文献</li> <li dataid="tworeferenceul">二级参考文献</li> <li dataid="twocitationul">二级引证文献</li> </ul> </div> <div class="reference_details" id="referenceList"> <ul id="referenceul"></ul> <ul id="citationul"></ul> <ul id="commonreferenceul"></ul> <ul id="commoncitationul"></ul> <ul id="tworeferenceul"></ul> <ul id="twocitationul"></ul> </div> </div> </div> <div class="literature cardcommon"> <div class="similarity "> <h3 class="all_title" id="enpatent66">相似文献</h3> <div class="similaritytab clearfix"> <ul> <li class="active" >外文文献</li> <li >中文文献</li> <li >专利</li> </ul> </div> <div class="similarity_details"> <ul > <li> <div> <b>1. </b><a class="enjiyixqcontent" href="/journal-foreign-detail/0704023734916.html">Further Insights in the Binding Mode of Selective Inhibitors to Human PDE4D Enzyme Combining Docking and Molecular Dynamics</a> <b>[J]</b> . <span> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=DUrsi Pasqualina&option=202" target="_blank" rel="nofollow" class="tuijian_auth tuijian_authcolor">DUrsi Pasqualina,</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Guariento Sara&option=202" target="_blank" rel="nofollow" class="tuijian_auth tuijian_authcolor">Guariento Sara,</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Trombetti Gabriele&option=202" target="_blank" rel="nofollow" class="tuijian_auth tuijian_authcolor">Trombetti Gabriele,</a> <a href="/journal-foreign-25225/" target="_blank" rel="nofollow" class="tuijian_authcolor">Molecular informatics .</a> <span>2016</span><span>,第8a9期</span> </span> </div> <p class="zwjiyix translation" style="max-width: initial;height: auto;word-break: break-all;white-space: initial;text-overflow: initial;overflow: initial;"> <span>机译：相结合对接和分子动力学的人PDE4D酶的选择性抑制剂结合模式的进一步见解</span> </p> </li> <li> <div> <b>2. </b><a class="enjiyixqcontent" href="/academic-journal-foreign_journal-molecular-modeling_thesis/0204110154162.html">Insight into the binding interactions of CYP450 aromatase inhibitors with their target enzyme: a combined molecular docking and molecular dynamics study</a> <b>[J]</b> . <span> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Roberta Galeazzi&option=202" target="_blank" rel="nofollow" class="tuijian_auth tuijian_authcolor">Roberta Galeazzi,</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Luca Massaccesi&option=202" target="_blank" rel="nofollow" class="tuijian_auth tuijian_authcolor">Luca Massaccesi </a> <a href="/journal-foreign-8018/" target="_blank" rel="nofollow" class="tuijian_authcolor">Journal of Molecular Modeling .</a> <span>2012</span><span>,第3期</span> </span> </div> <p class="zwjiyix translation" style="max-width: initial;height: auto;word-break: break-all;white-space: initial;text-overflow: initial;overflow: initial;"> <span>机译：深入了解CYP450芳香酶抑制剂与目标酶的结合相互作用：结合的分子对接和分子动力学研究</span> </p> </li> <li> <div> <b>3. </b><a class="enjiyixqcontent" href="/academic-journal-foreign_molecular-biosystems_thesis/020418274864.html">Insights into the binding modes of CC chemokine receptor 4 (CCR4) inhibitors: a combined approach involving homology modelling, docking, and molecular dynamics simulation studies</a> <b>[J]</b> . <span> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Changdev G. Gadhe&option=202" target="_blank" rel="nofollow" class="tuijian_auth tuijian_authcolor">Changdev G. Gadhe,</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Mi-hyun Kim&option=202" target="_blank" rel="nofollow" class="tuijian_auth tuijian_authcolor">Mi-hyun Kim </a> <a href="/journal-foreign-4322/" target="_blank" rel="nofollow" class="tuijian_authcolor">Molecular BioSystems .</a> <span>2015</span><span>,第2期</span> </span> </div> <p class="zwjiyix translation" style="max-width: initial;height: auto;word-break: break-all;white-space: initial;text-overflow: initial;overflow: initial;"> <span>机译：深入了解CC趋化因子受体4（CCR4）抑制剂的结合模式：涉及同源性建模，对接和分子动力学模拟研究的组合方法</span> </p> </li> <li> <div> <b>4. </b><a class="enjiyixqcontent" href="/academic-conference-foreign_meeting-194646_thesis/020513177643.html">Probing ligand binding modes of human cytochrome P45O SJS by homology modeling, molecular dynamics simulation,and flexible molecular docking</a> <b>[C]</b> . <span> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Weihua Li&option=202" target="_blank" rel="nofollow" class="tuijian_auth tuijian_authcolor">Weihua Li,</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Yun Tang&option=202" target="_blank" rel="nofollow" class="tuijian_auth tuijian_authcolor">Yun Tang,</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Hong Liu&option=202" target="_blank" rel="nofollow" class="tuijian_auth tuijian_authcolor">Hong Liu,</a> <a href="/conference-foreign-194646/" target="_blank" rel="nofollow" class="tuijian_authcolor">第四届国际分子模拟与信息技术应用学术会议（The 4th International Conference of Molecular Simulations and Applied Informatics Technologies）论文集 .</a> <span>2008</span> </span> </div> <p class="zwjiyix translation" style="max-width: initial;height: auto;word-break: break-all;white-space: initial;text-overflow: initial;overflow: initial;"> <span>机译：通过同源性建模，分子动力学模拟和灵活的分子对接来探索人细胞色素P45O SJS的配体结合模式</span> </p> </li> <li> <div> <b>5. </b><a class="enjiyixqcontent" href="/academic-degree-foreign_mphd_thesis/02061592564.html">Combination of the Computational Methods: Molecular dynamics, Homology Modeling and Docking to Design Novel Inhibitors and Study Structural Changes in Target Proteins for Current Diseases.</a> <b>[D] </b> . <span> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Parra, Katherine.&option=202" target="_blank" rel="nofollow" class="tuijian_auth tuijian_authcolor">Parra, Katherine. </a> <span>2014</span> </span> </div> <p class="zwjiyix translation" style="max-width: initial;height: auto;word-break: break-all;white-space: initial;text-overflow: initial;overflow: initial;"> <span>机译：计算方法的组合：分子动力学，同源性建模和对接，以设计新型抑制剂并研究当前疾病靶蛋白的结构变化。</span> </p> </li> <li> <div> <b>6. </b><a class="enjiyixqcontent" href="/academic-journal-foreign-pmc_wiley-blackwell-online-open_thesis/040005029476.html">Further Insights in the Binding Mode of Selective Inhibitors to Human PDE4D Enzyme Combining Docking and Molecular Dynamics</a> <b>[O] </b> . <span> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Pasqualina DUrsi&option=202" target="_blank" rel="nofollow" class="tuijian_auth tuijian_authcolor">Pasqualina DUrsi,</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Sara Guariento&option=202" target="_blank" rel="nofollow" class="tuijian_auth tuijian_authcolor">Sara Guariento,</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Gabriele Trombetti&option=202" target="_blank" rel="nofollow" class="tuijian_auth tuijian_authcolor">Gabriele Trombetti,</a> <span>-1</span> </span> </div> <p class="zwjiyix translation" style="max-width: initial;height: auto;word-break: break-all;white-space: initial;text-overflow: initial;overflow: initial;"> <span>机译：选择性抑制剂对人PDE4D酶结合对接和分子动力学的结合模式的进一步见解。</span> </p> </li> <li> <div> <b>7. </b><a class="enjiyixqcontent" href="/open-access_resources_thesis/0100034444038.html ">Further Insights in the Binding Mode of Selective Inhibitors to Human PDE4D Enzyme Combining Docking and Molecular Dynamics</a> <b>[O] </b> . <span> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=D'Ursi, Pasqualina&option=202" target="_blank" rel="nofollow" class="tuijian_auth tuijian_authcolor">D'Ursi, Pasqualina,</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Guariento, Sara&option=202" target="_blank" rel="nofollow" class="tuijian_auth tuijian_authcolor">Guariento, Sara,</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Trombetti, Gabriele&option=202" target="_blank" rel="nofollow" class="tuijian_auth tuijian_authcolor">Trombetti, Gabriele,</a> <span>2016</span> </span> </div> <p class="zwjiyix translation" style="max-width: initial;height: auto;word-break: break-all;white-space: initial;text-overflow: initial;overflow: initial;"> <span>机译：选择性抑制剂对人PDE4D酶结合对接和分子动力学的结合模式的进一步见解。</span> </p> </li> </ul> <ul style="display: none;"> <li> <div> <b>1. </b><a class="enjiyixqcontent" href="/academic-journal-cn_acta-physico-chimica-sinica_thesis/0201251035813.html">分子对接打分修正及在内皮脂肪酶选择性抑制剂筛选中的应用</a> <b>[J]</b> <span> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=罗棋耀&option=202" target="_blank" rel="nofollow" class="tuijian_auth tuijian_authcolor"> . 罗棋耀</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=王紫鋆&option=202" target="_blank" rel="nofollow" class="tuijian_auth tuijian_authcolor">,王紫鋆</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=金宏威&option=202" target="_blank" rel="nofollow" class="tuijian_auth tuijian_authcolor">,金宏威</a> <span> <a href="/journal-cn-15102/" target="_blank" rel="nofollow" class="tuijian_authcolor"> . 物理化学学报 </a> </span> <span> . 2016</span><span>,第010期</span> </span> </div> </li> <li> <div> <b>2. </b><a class="enjiyixqcontent" href="/academic-journal-cn_chemical-journal-chinese-universities_thesis/0201231541926.html">血管紧张素转换酶与抑制肽结合模式的分子动力学研究</a> <b>[J]</b> <span> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=王嵩&option=202" target="_blank" rel="nofollow" class="tuijian_auth tuijian_authcolor"> . 王嵩</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=管珊珊&option=202" target="_blank" rel="nofollow" class="tuijian_auth tuijian_authcolor">,管珊珊</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=万永凤&option=202" target="_blank" rel="nofollow" class="tuijian_auth tuijian_authcolor">,万永凤</a> <span> <a href="/journal-cn-10958/" target="_blank" rel="nofollow" class="tuijian_authcolor"> . 高等学校化学学报 </a> </span> <span> . 2017</span><span>,第007期</span> </span> </div> </li> <li> <div> <b>3. </b><a class="enjiyixqcontent" href="/academic-journal-cn_journal-zhejiang-university-science-edition_thesis/0201248234056.html">乙酰乳酸合成酶与抑制剂ZJ0777及CIE的分子对接和分子动力学模拟</a> <b>[J]</b> <span> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=汪冒君&option=202" target="_blank" rel="nofollow" class="tuijian_auth tuijian_authcolor"> . 汪冒君</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=宣南霞&option=202" target="_blank" rel="nofollow" class="tuijian_auth tuijian_authcolor">,宣南霞</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=吴军&option=202" target="_blank" rel="nofollow" class="tuijian_auth tuijian_authcolor">,吴军</a> <span> <a href="/journal-cn-4535/" target="_blank" rel="nofollow" class="tuijian_authcolor"> . 浙江大学学报（理学版） </a> </span> <span> . 2015</span><span>,第006期</span> </span> </div> </li> <li> <div> <b>4. </b><a class="enjiyixqcontent" href="/academic-journal-cn_chemistry-bioengineering_thesis/0201246503142.html">基于分子对接技术研究漆酶与介质间的r结合模式与相互作用机制</a> <b>[J]</b> <span> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=陶国翔&option=202" target="_blank" rel="nofollow" class="tuijian_auth tuijian_authcolor"> . 陶国翔</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=李爱秀&option=202" target="_blank" rel="nofollow" class="tuijian_auth tuijian_authcolor">,李爱秀</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=封加栋&option=202" target="_blank" rel="nofollow" class="tuijian_auth tuijian_authcolor">,封加栋</a> <span> <a href="/journal-cn-9126/" target="_blank" rel="nofollow" class="tuijian_authcolor"> . 化学与生物工程 </a> </span> <span> . 2016</span><span>,第012期</span> </span> </div> </li> <li> <div> <b>5. </b><a class="enjiyixqcontent" href="/academic-degree-domestic_mphd_thesis/020315244447.html">分子对接与分子动力学探究表面活性剂对漆酶降解苯酚的作用机理</a> <b>[A] </b> <span> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=刘玉杰&option=202" target="_blank" rel="nofollow" class="tuijian_auth tuijian_authcolor"> . 刘玉杰</a> <span> . 2019</span> </span> </div> </li> </ul> <ul style="display: none;"> <li> <div> <b>1. </b><a class="enjiyixqcontent" href="/patent-detail/06130401552542.html">TARGET MOLECULE-LIGAND BINDING MODE PREDICTION COMBINING DEEP LEARNING-BASED INFORMATICS WITH MOLECULAR DOCKING</a> <b>[P]</b> . <span> 外国专利：  US2020342953A1 </span> <span> . 2020-10-29</span> </div> <p class="zwjiyix translation" style="max-width: initial;height: auto;word-break: break-all;white-space: initial;text-overflow: initial;overflow: initial;"> <span>机译：基于深度学习的信息与分子对接相结合的目标分子配体结合模式预测 </span> </p> </li> <li> <div> <b>2. </b><a class="enjiyixqcontent" href="/patent-detail/06130403909947.html">A THEORETICAL STUDY AND A COMPUTER-ASSISTED QUANTOMOLECULAR DESIGN OF ANTICANCER CHEMICAL HYPER-PHARMACOPHORICAL COMPOUNDS AGAINST SIGNAL TRANSDUCTION PEPTIDE TARGETS-MOLECULES AND MOTIF REGIONS THEREOF WITH MODELLING TECHNIQUES, MOLECULAR RECOGNITION AND MOLECULAR DYNAMICS FOR THE FIGHTING OF THE GLIOMA DISEASE IN HUMANS</a> <b>[P]</b> . <span> 外国专利：  GR20180200061U </span> <span> . 2019-05-24</span> </div> <p class="zwjiyix translation" style="max-width: initial;height: auto;word-break: break-all;white-space: initial;text-overflow: initial;overflow: initial;"> <span>机译：建模方法，分子识别，分子识别的抗肿瘤化学肽类化合物分子信号和分子区的理论研究和计算机辅助量子分子设计 </span> </p> </li> <li> <div> <b>3. </b><a class="enjiyixqcontent" href="/patent-detail/06130407117632.html">Discovery of FDA-approved drugs as inhibitors of fatty acid binding protein 4 using molecular docking screening</a> <b>[P]</b> . <span> 外国专利：  US9968616B2 </span> <span> . 2018-05-15</span> </div> <p class="zwjiyix translation" style="max-width: initial;height: auto;word-break: break-all;white-space: initial;text-overflow: initial;overflow: initial;"> <span>机译：使用分子对接筛选发现FDA批准的脂肪酸结合蛋白4抑制剂药物 </span> </p> </li> </ul> </div> </div> </div> <div class="theme cardcommon" style="overflow: auto;display:none"> <h3 class="all_title" id="enpatent55">相关主题</h3> <ul id="subject"> </ul> </div> </div> </div> </div> <div class="right rightcon"> <div class="details_img cardcommon clearfix" style="margin-bottom: 10px;display:none;" > </div> </div> </div> <div id="thesis_get_original1" class="downloadBth" style="bottom: 19px;z-index: 999;" onclick="ywcd('0704023734916','4',7,2,1,'',this,24)" class="delivery" prompt="010401" title="通过人工服务将文献原文发送至邮箱" >获取原文</div> <div class="journalsub-pop-up" style="display: none"> <div class="journal-sub"> <h2>期刊订阅</h2> <img src="https://cdn.zhangqiaokeyan.com/img/loginclose.png" alt="关闭" onclick="$('.journalsub-pop-up').hide()"> <p class="pardon">抱歉，该期刊暂不可订阅，敬请期待！</p> <p class="current">目前支持订阅全部北京大学中文核心（2020）期刊目录。</p> <div style="display: flex;margin-top: 69px;justify-content: space-between;"> <div class="no-sub" onclick="$('.journalsub-pop-up').hide()">暂不订阅</div> <div class="other-sub" onclick="continueSub('from=pc-detail')">继续订阅其他期刊</div> </div> </div> </div> <div class="right_btn"> <ul> <li class="gouwuche">  </li> <li class="yijian"> <a href="javascript:void(0);" onclick="link_analysis('/mycenter/auth/complaint.html',this)" title="意见反馈">意见反馈</a> </li> <li class="top"> <a href="javascript:scrollTo(0,0);" title="回到顶部">回到顶部</a> </li> <li class="shouye"> <a href="/" title="首页">回到首页</a> </li> </ul> </div> <div class="xllindexfooter"> <div class="xllindexfootercenter"> <div class="xllindexfooterleft left" > <div class="xllindexfooterleftli"> <ul> <li><a href="/about.html" title="关于掌桥">关于掌桥</a></li> <li><a href="/help/helpmap.html" title="资源导航">资源导航</a></li> <li><a href="/help/helpguide.html" title="新手指南">新手指南</a></li> <li><a href="/help/helpcenter.html" title="常见问题">常见问题</a></li> <li><a href="/sitemap.html" title="网站地图">网站地图</a></li> <li><a href="/help/helpcenter.html?type=9" title="版权声明">版权声明</a></li> </ul> </div> <div class="xllindexfooterleft"> <p class="xllindexfooterlefteamil">客服邮箱：kefu@zhangqiaokeyan.com</p> <div class="xllindexfooterlefttcp"> <div class="xllindexfooterpoliceiimg"></div> <div class="xllindexfooterpoliceispan"> <span>京公网安备：11010802029741号 </span> <span>ICP备案号：<a href="https://beian.miit.gov.cn" rel="nofollow" target="_blank" title="ICP备案号">京ICP备15016152号-6</a></span> <span>六维联合信息科技 (北京) 有限公司©版权所有</span> </div> </div> </div> </div> <div class="xllindexfooterright left"> <ul> <li> <p style="font-weight: bold;">客服微信</p> <div></div> </li> <li> <p style="font-weight: bold;">服务号</p> <div></div> </li> </ul> </div> </div> </div> <span id="0704023734916down" data-source="7," data-out-id="PgC3DjsxaCCPJqwjSeXHVQ==," data-f-source-id="7" data-title="Further Insights in the Binding Mode of Selective Inhibitors to Human PDE4D Enzyme Combining Docking and Molecular Dynamics" data-price="20" data-site-name="" data-transnum="24" style="display:none;"></span> <input type="hidden" value="4" id="sourcetype"> <input type="hidden" value="0704023734916" id="docid"> <input type="hidden" value="25225" id="journalid"> <input type="hidden" value="1" id="inyn_provide_service_level"> <input type="hidden" value="https://cdn.zhangqiaokeyan.com" id="imgcdn"> <input type="hidden" value="1" id="isdeatail"> <input type="hidden" value="" id="syyn_indexed_database"> <input type="hidden" value="" id="servicetype"> <input type="hidden" id="pagename" value="Further Insights in the Binding Mode of Selective Inhibitors to Human PDE4D Enzyme Combining Docking and Molecular Dynamics"/> <input type="hidden" value="thesis_get_original" id="pageIdentification"> <script type="text/javascript" src="https://cdn.zhangqiaokeyan.com/js/jquery-1.12.4.js"></script> <script type="text/javascript" src="https://cdn.zhangqiaokeyan.com/js/common/lwlh_ajax.js"></script> <script type="text/javascript" src="https://cdn.zhangqiaokeyan.com/js/zq.js?v=5.8.7"></script> <script type="text/javascript" src="https://cdn.zhangqiaokeyan.com/js/common/common.js?v=5.8.7"></script> <script type="text/javascript" src="https://cdn.zhangqiaokeyan.com/js/jquery.cookie.js"></script> <script type="text/javascript" src="https://cdn.zhangqiaokeyan.com/js/top.js?v=5.8.7"></script> <script type="text/javascript" src="https://cdn.zhangqiaokeyan.com/js/common/tip.js?v=5.8.7"></script> <script type="text/javascript" src="https://cdn.zhangqiaokeyan.com/js/common/login.js?v=5.8.7"></script> <script type="text/javascript" src="https://cdn.zhangqiaokeyan.com/js/common/down.js?v=5.8.7"></script> <script type="text/javascript" src="https://cdn.zhangqiaokeyan.com/js/common/search.js?v=5.8.7"></script> <script type="text/javascript" src="https://cdn.zhangqiaokeyan.com/js/common/newmail.js?v=5.8.7"></script> <script type="text/javascript" src="https://cdn.zhangqiaokeyan.com/js/common/page.js?v=5.8.7"></script> <script type="text/javascript" src="https://cdn.zhangqiaokeyan.com/js/searchtype.js?v=5.8.7"></script> <script type="text/javascript" src="https://cdn.zhangqiaokeyan.com/js/user/regist.js?v=5.8.7"></script> <script type="text/javascript" src="https://cdn.zhangqiaokeyan.com/js/zxs_solor/detail.js?v=5.8.7"></script> <script type="text/javascript" src="https://cdn.zhangqiaokeyan.com/js/zxs_solor/reference.js?v=5.8.7"></script> <script type="text/javascript" src="https://www.zhangqiaokeyan.com/statistics/static/pagecollection.js"></script> <script type="text/javascript" src="https://cdn.zhangqiaokeyan.com/js/tj.js"></script> <script type="text/javascript" src="https://cdn.zhangqiaokeyan.com/js/common/sse.js?v=5.8.7"></script> <script type="text/javascript" src="https://cdn.zhangqiaokeyan.com/js/pushbaidu.js"></script> <script type="text/javascript" src="https://cdn.zhangqiaokeyan.com/js/common/history.js"></script> <script type="text/javascript" src="https://cdn.zhangqiaokeyan.com/js/util/cookie.js?v=5.8.7"></script> <script type="text/javascript" src="https://cdn.zhangqiaokeyan.com/js/weipu/weipu.js?v=5.8.7"></script> </body> <script> function kefu(customization) { var from = GetQueryString("from"); if (from == null || from == "") { from = "other"; } var url = getWxWorkQrCode(73, from, customization); if (url == "" || typeof url == 'undefined') { url = "https://wework.qpic.cn/wwpic/994838_0LUTS-VqR0quT1N_1675665967/0"; } tipDocGuidance(url, '人工辅助获取外文期刊材料'); } $(function(){ var weiPuStatus = getCookie('WeiPuStatus'); if(weiPuStatus){ tipWeiPuStatus(weiPuStatus); delCookie('WeiPuStatus'); } getFacetKeywordVoInId(); var sourcetype = $("#sourcetype").val(); var inyn_provide_service_level = $("#inyn_provide_service_level").val(); if((sourcetype ==1||sourcetype==4)&&inyn_provide_service_level!=4){ getJournal(); } }) function toCoverPage(){ var sourcetype=$("#sourcetype").val var fromStr=""; if(sourcetype==0){ fromStr="pc-wwoaxiangqing"; } if(sourcetype==4){ fromStr="pc-wwdetail-title"; } if(sourcetype==5){ fromStr="pc-wwhuiyixiangqing"; } window.location.href=url+"/zhichengpingshenlunwen.html?from="+fromStr; } </script> </html>