The in silico identification of small molecules for protein-protein interaction inhibition in AKAP-Lbc-RhoA signaling complex
文献类型：期刊论文
| 作者 | Khan, Asifullah1,2; Munir, Mehwish2; Aiman, Sara2; Wadood, Abdul2; Khan, Arif-ullah3; , |
| 刊名 | COMPUTATIONAL BIOLOGY AND CHEMISTRY
 |
| 出版日期 | 2017 |
| 卷号 | 67期号:-页码:84-91 |
| 关键词 | AKAP-Lbc Protein -protein interaction inhibitors Molecular docking Drug designing |
| ISSN号 | 1476-9271 |
| DOI | 10.1016/j.compbiolchem.2016.12.014 |
| 文献子类 | Article |
| 英文摘要 | The rational design of small molecules that mimic key residues at the interface of interacting proteins can be a successful approach to target certain biological signaling cascades causing pathophysiological outcome. The A-Kinase Anchoring Protein, i.e. AKAP-Lbc, catalyses nucleotide exchange on RhoA and is involved in cardiac repolarization. The oncogenic AKAP-Lbc induces the RhoA GTPase hyperactivity and aberrantly amplifies the signaling pathway leading to hypertrophic cardiomyocytes. We took advantage of the AKAP-Lbc-RhoA complex crystal structure to design in silico small molecules predicted to inhibit the associated pathological signaling cascade. We adopted the strategies of pharmacophore building, virtual screening and molecular docking to identify the small molecules capable to target AKAP-Lbc and RhoA interactions. The pharmacophore model based virtual screening unveils two lead compounds from the TIMBAL database of small molecules modulating the targeted protein-protein interactions. The molecular docking analysis revealed the lead compounds ' potentialities to establish the essential chemical interactions with the key interactive residues of the complex. These features provided a road map for designing additional potent chemical derivatives and fragments of the original lead compounds to perturb the AKAP-Lbc and RhoA interactions. Experimental validations may elucidate the therapeutic potential of these lead chemical scaffolds to deal with aberrant AKAP-Lbc signaling based cardiac hypertrophy. (C) 2016 Elsevier Ltd. All rights reserved. |
| 学科主题 | Life Sciences & Biomedicine - Other Topics ; Computer Science |
| WOS关键词 | DRUG TARGETS ; KINASE-A ; ONCOGENE ; DH |
| 语种 | 英语 |
| WOS记录号 | WOS:000395598000009 |
| 出版者 | ELSEVIER SCI LTD |
| 版本 | 出版稿 |
| 源URL | [http://202.127.25.144/handle/331004/812]  |
| 专题 | 中国科学院上海生命科学研究院营养科学研究所 |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Biol Sci, CAS MPG Partner Inst Computat Biol PICB, CAS Key Lab Computat Biol, Shanghai 200031, Peoples R China; 2.Abdul Wali Khan Univ Mardan, Dept Biochem, Mardan 23200, Pakistan; 3.Ripha Int Univ, Ripha Inst Pharmaceut Sci, Islamabad, Pakistan, |
| 推荐引用方式 GB/T 7714 | Khan, Asifullah,Munir, Mehwish,Aiman, Sara,et al. The in silico identification of small molecules for protein-protein interaction inhibition in AKAP-Lbc-RhoA signaling complex[J]. COMPUTATIONAL BIOLOGY AND CHEMISTRY,2017,67(-):84-91. |
| APA | Khan, Asifullah,Munir, Mehwish,Aiman, Sara,Wadood, Abdul,Khan, Arif-ullah,&,.(2017).The in silico identification of small molecules for protein-protein interaction inhibition in AKAP-Lbc-RhoA signaling complex.COMPUTATIONAL BIOLOGY AND CHEMISTRY,67(-),84-91. |
| MLA | Khan, Asifullah,et al."The in silico identification of small molecules for protein-protein interaction inhibition in AKAP-Lbc-RhoA signaling complex".COMPUTATIONAL BIOLOGY AND CHEMISTRY 67.-(2017):84-91. |
入库方式： OAI收割
来源：上海营养与健康研究所
浏览0
下载0
收藏0
其他版本
除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。