Structural Studies and Structure Activity Relationships for Novel Computationally Designed Non-nucleoside Inhibitors and Their Interactions With HIV-1 Reverse Transcriptase.
Structural Studies and Structure Activity Relationships for Novel Computationally Designed Non-nucleoside Inhibitors and Their Interactions With HIV-1 Reverse Transcriptase.
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DOI：
10.3389/fmolb.2022.805187
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发表时间：
2022
影响因子：
5
通讯作者：
Anderson KS
中科院分区：
文献类型：
--
作者：
Frey KM;Bertoletti N;Chan AH;Ippolito JA;Bollini M;Spasov KA;Jorgensen WL;Anderson KS
来自人类免疫缺陷病毒的逆转录酶（RT）仍然是抗逆转录病毒治疗的有吸引力的药物靶标。2022年6月将纪念第一个人类免疫缺陷病毒（HIV）RT晶体结构复合物30周年，该复合物是用非核苷逆转录酶抑制剂奈韦拉平解决的。这种结构的释放为设计许多非核苷逆转录酶抑制剂（NNRTI）家族提供了机会。在致敬的第一个RT-奈韦拉平结构，我们已经开发了几个化合物类靶向HIV RT的非核苷抑制剂结合口袋。RT的晶体结构的广泛分析复杂的化合物通知迭代的结构为基础的药物设计。七个额外的复合物的结构进行了测定和分析，总结关键的相互作用与残基的非核苷抑制剂结合口袋（NNIBP）的RT。额外的见解与抗病毒的数据和分子动力学模拟结果比较结构阐明关键的相互作用和动态之间的核苷酸和非核苷结合位点。
Reverse transcriptase (RT) from the human immunodeficiency virus continues to be an attractive drug target for antiretroviral therapy. June 2022 will commemorate the 30th anniversary of the first Human Immunodeficiency Virus (HIV) RT crystal structure complex that was solved with non-nucleoside reverse transcriptase inhibitor nevirapine. The release of this structure opened opportunities for designing many families of non-nucleoside reverse transcriptase inhibitors (NNRTIs). In paying tribute to the first RT-nevirapine structure, we have developed several compound classes targeting the non-nucleoside inhibitor binding pocket of HIV RT. Extensive analysis of crystal structures of RT in complex with the compounds informed iterations of structure-based drug design. Structures of seven additional complexes were determined and analyzed to summarize key interactions with residues in the non-nucleoside inhibitor binding pocket (NNIBP) of RT. Additional insights comparing structures with antiviral data and results from molecular dynamics simulations elucidate key interactions and dynamics between the nucleotide and non-nucleoside binding sites.
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影响因子：
7.3
作者：
Frey KM;Puleo DE;Spasov KA;Bollini M;Jorgensen WL;Anderson KS
通讯作者：
Anderson KS
DOI：
10.1107/s0907444909052925
发表时间：
2010-02
期刊：
Acta crystallographica. Section D, Biological crystallography
影响因子：
--
作者：
Adams PD;Afonine PV;Bunkóczi G;Chen VB;Davis IW;Echols N;Headd JJ;Hung LW;Kapral GJ;Grosse-Kunstleve RW;McCoy AJ;Moriarty NW;Oeffner R;Read RJ;Richardson DC;Richardson JS;Terwilliger TC;Zwart PH
通讯作者：
Zwart PH
影响因子：
7.3
作者：
Bollini, Mariela;Domaoal, Robert A.;Thakur, Vinay V.;Gallardo-Macias, Ricardo;Spasov, Krasimir A.;Anderson, Karen S.;Jorgensen, William L.
通讯作者：
Jorgensen, William L.
DOI：
10.3390/v6104095
发表时间：
2014-10-24
期刊：
Viruses
影响因子：
--
作者：
Iyidogan P;Anderson KS
通讯作者：
Anderson KS
DOI：
10.1107/s0907444909042073
发表时间：
2010-01
期刊：
Acta crystallographica. Section D, Biological crystallography
影响因子：
--
作者：
Chen VB;Arendall WB 3rd;Headd JJ;Keedy DA;Immormino RM;Kapral GJ;Murray LW;Richardson JS;Richardson DC
通讯作者：
Richardson DC