Archive for the ‘Hot Articles’ Category

Unravelling the mechanism of allosteric hepatitis C virus inhibition – a new HOT article

New insights into how the spread of hepatitis C virus (HCV) can be prevented using an enzyme inhibitor have been reported in Molecular BioSystems.

Free and bound protein

Motion modes of the free and bound protein from PCA analysis

Hai-Feng Chen’s group at Shanghai Jiaotong University used molecular dynamics to study the effect of a cyclopropylindolobenzazepine derivative, M2. The technique was used to model just how M2 suppressed a key viral protein, NS5B, to stop the virus from replicating.

M2 is known to be an efficient and highly specific HCV inhibitor. Because the enzyme it targets has no mammalian equivalent, it could be used to fight viral infection without any risk of it adversely affecting any important human enzymes. However, exactly how its inhibition works isn’t yet known.

The group found that when M2 bound to NS5B it caused a conformational change through an allosteric mechanism, changing it from an “open” to a “closed” form. This change destabilised the enzyme, altering information transfer from the substrate binding site to the catalytic domain and drastically weakening its effect. The M2-bound enzyme had greater structural variation – particularly in its A1 loop – indicating its lack of stability.

The allosteric mechanism was confirmed by testing a weakened form of M2, which had significantly less effect on the connectivity of the enzyme than the normal version. A further in vitro resistance study reinforced this by comparing the normal enzyme to a mutant version with a truncated A1 loop. Inhibition of the mutant version was far less effective than that of the wild type, highlighting the importance of the A1 loop in the inhibition mechanism.

Understanding exactly how M2 inhibits viral NS5B, and how mutated forms of the virus might resist this, is vital – it could in future lead to new and more effective drugs to fight HCV.


Read the full article here:

Allosteric mechanism of cyclopropylindolobenzazepine inhibitors for HCV NS5B RdRp via dynamic correlation network analysis
Mueed ur Rahman, Hao Liu, Abdul Wadood and Hai-Feng Chen
Mol. BioSyst., 2016, Advance Article
DOI: 10.1039/C6MB00521G


Susannah May is a guest web writer for the RSC Journal blogs. She currently works in the Publishing Department of the Royal Society of Chemistry, and has a keen interest in biology and biomedicine, and the frontiers of    their intersection with chemistry. She can be found on Twitter using @SusannahCIMay.

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Unravelling a knotty problem: A simulation study of neurotoxic knotted proteins

Knotted proteins and their part in neurodegenerative diseases such as Huntington’s and spinal muscular atrophy have been put under scrutiny in a new HOT article recently published in Molecular Biosystems.

Two example trajectories that lead to the translocation of knotted species (yellow). Left: translocation of 1J85 when pulled in the I-N protocol. Right: unfolding of a HTT60 knotted conformation (polyQ part = red).

It’s long been known that aggregations of certain proteins have a key role in many neurodegenerative diseases, including Alzheimer’s, Parkinson’s and Huntington’s. However, exactly how these aggregations happen and how it causes disease is still a subject of intense study.

Marek Cieplak’s group at the Polish University of Sciences have used mathematical simulations to study this still-mysterious phenomenon. They looked at huntingtin, a protein involved in embryonic development. If this protein mutates, it can cause neurodegenerative diseases such as Huntington’s by forming toxic oligomers and amyloid fibres. Recent evidence has suggested that monomer forms of the protein could also be neurotoxic – Cieplak’s group theorise that this is due to knots in the structure of the protein that prevent neurodegeneration by the proteasome.

The group used mathematical simulations to create theoretical models of the knotted protein and the proteasome, and investigated the effect that the former would have on the latter under different conditions of force. Their results point to the knots being responsible for the jamming of the proteasome’s degradation mechanism. Under certain conditions proteins would stay knotted instead of untying, hindering normal neurodegeneration and leading to neurotoxic build-up of proteins.

The results will help to provide greater understanding of the mechanisms behind genetic diseases such as Huntington’s, paving the way for future experimental studies and, hopefully one day, the development of new and effective treatments.


Read the full article here:

Unfolding knots by proteasome-like systems: simulations of the behaviour of folded and neurotoxic proteins
Michał Wojciechowski, Àngel Gómez-Sicilia, Mariano Carrión-Vázquez and Marek Cieplak
DOI: 10.1039/C6MB00214E




Susannah May is a guest web writer for the RSC Journal blogs. She currently works in the Publishing Department of the Royal Society of Chemistry, and has a keen interest in biology and biomedicine, and the frontiers of their intersection with chemistry. She can be found on Twitter using @SusannahCIMay.

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Recent HOT Molecular BioSystems articles

The following HOT articles have been highlighted by the reviewers of the articles as being particularly interesting or significant pieces of research. These are all free to access until 28th February 2015. The order they appear in the list has no meaning or ranking.


Applications of mass spectrometry for cellular lipid analysis
Chunyan Wang, Miao Wang and Xianlin Han 
DOI: 10.1039/C4MB00586D, Review Article

C4MB00586D GA


Systems biology approach to understanding post-traumatic stress disorder
Gunjan S. Thakur, Bernie J. Daigle Jr, Kelsey R. Dean, Yuanyang Zhang, Maria Rodriguez-Fernandez, Rasha Hammamieh, Ruoting Yang, Marti Jett, Joseph Palma, Linda R. Petzold and Francis J. Doyle III 
DOI: 10.1039/C4MB00404C, Review Article

C4MB00404C GA


An integrated analysis of differential miRNA and mRNA expressions in human gallstones
Bin Yang, Bin Liu, Pinduan Bi, Tao Wu, Qiang Wang and Jie Zhang 
DOI: 10.1039/C4MB00741G, Paper

C4MB00741G GA


Hierarchical control of coherent gene clusters defines the molecular mechanisms of glioblastoma
Igor F. Tsigelny, Valentina L. Kouznetsova, Pengfei Jiang, Sandeep C. Pingle and Santosh Kesari 
DOI: 10.1039/C5MB00007F, Paper

C5MB00007F GA


Cancer-associated fibroblasts induce trastuzumab resistance in HER2 positive breast cancer cells
Yan Mao, Yuzi Zhang, Qing Qu, Meizhong Zhao, Ying Lou, Junjun Liu, Ou huang, Xiaosong Chen, Jiayi Wu and Kunwei Shen 
DOI: 10.1039/C4MB00710G, Paper

C4MB00710G GA


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Recent HOT Molecular BioSystems articles

The following HOT articles have been highlighted by the reviewers of the articles as being particularly interesting or significant pieces of research. These are all free to access until 31st January 2015. The order they appear in the list has no meaning or ranking.

Cysteine-mediated redox signalling in the mitochondria
D. W. Bak and E. Weerapana 
DOI: 10.1039/C4MB00571F, Review Article

C4MB00571F GA


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Recent HOT Molecular BioSystems articles

The following HOT articles have been highlighted by the reviewers of the articles as being particularly interesting or significant pieces of research. These are all free to access until 31st December 2014. The order they appear in the list has no meaning or ranking.

 Fatty acid biosynthesis revisited: structure elucidation and metabolic engineering
Joris Beld, D. John Lee and Michael D. Burkart 
DOI: 10.1039/C4MB00443D, Review Article

C4MB00443D GA


Studies of N9-arenthenyl purines as novel DFG-in and DFG-out dual Src/Abl inhibitors using 3D-QSAR, docking and molecular dynamics simulations
Shaojie Ma, Guohua Zeng, Danqing Fang, Juping Wang, Wenjuan Wu, Wenguo Xie, Shepei Tan and Kangcheng Zheng 
DOI: 10.1039/C4MB00350K, Paper
C4MB00350K GA

C4MB00457D GA

Identification of cancer-related lncRNAs through integrating genome, regulome and transcriptome features
Tingting Zhao, Jinyuan Xu, Ling Liu, Jing Bai, Chaohan Xu, Yun Xiao, Xia Li and Liming Zhang 
DOI: 10.1039/C4MB00478G, Paper
C4MB00478G GA

UHPLC-LTQ-Orbitrap MS combined with spike-in method for plasma metabonomics analysis of acute myocardial ischemia rats and pretreatment effect of Danqi Tongmai tablet
Bingpeng Yan, Yanping Deng, Jinjun Hou, Qirui Bi, Min Yang, Baohong Jiang, Xuan Liu, Wanying Wu and Dean Guo 
DOI: 10.1039/C4MB00529E, Paper
C4MB00529E GA

A metabolomic and pharmacokinetic study on the mechanism underlying the lipid-lowering effect of orally administered berberine
Shenghua Gu, Bei Cao, Runbin Sun, Yueqing Tang, Janice L. Paletta, Xiao-Lei Wu, Linsheng Liu, Weibin Zha, Chunyan Zhao, Yan Li, Jason M. Radlon, Phillip B. Hylemon, Huiping Zhou, Jiye Aa and Guangji Wang 
DOI: 10.1039/C4MB00500G, Paper

C4MB00500G GA


Modeling the mitotic regulatory network identifies highly efficient anti-cancer drug combinations
Yiran Wu, Xiaolong Zhuo, Ziwei Dai, Xiao Guo, Yao Wang, Chuanmao Zhang and Luhua Lai 
DOI: 10.1039/C4MB00610K, Paper

C4MB00610K GA


Prediction of advanced ovarian cancer recurrence by plasma metabolic profiling
Haiyu Zhang, Tingting Ge, Xiaoming Cui, Yan Hou, Chaofu Ke, Meng Yang, Kai Yang, Jingtao Wang, Bing Guo, Fan Zhang, Ge Lou and Kang Li 
DOI: 10.1039/C4MB00407H, Paper

C4MB00407H GA


A pre-structured helix in the intrinsically disordered 4EBP1
Do-Hyoung Kim, Chewook Lee, Ye-Jin Cho, Si-Hyung Lee, Eun-Ji Cha, Ji-Eun Lim, T. Michael Sabo, Christian Griesinger, Donghan Lee and Kyou-Hoon Han 
DOI: 10.1039/C4MB00532E, Communication

C4MB00532E GA

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Recent HOT Molecular BioSystems articles

The following HOT articles have been highlighted by the reviewers of the articles as being particularly interesting or significant pieces of research. These are all free to access until 30th November. The order they appear in the list has no meaning or ranking.

Systems biosynthesis of secondary metabolic pathways within the oral human microbiome member Streptococcus mutans
Rostyslav Zvanych, Nikola Lukenda, Xiang Li, Janice J. Kim, Satheeisha Tharmarajah and Nathan A. Magarvey
DOI: 10.1039/C4MB00406J, Paper

Systems biosynthesis of secondary metabolic pathways


Structural mass spectrometry of tissue extracts to distinguish cancerous and non-cancerous breast diseases
Kelly M. Hines, Billy R. Ballard, Dana R. Marshall and John A. McLean
DOI: 10.1039/C4MB00250D, Paper

Structural mass spectrometry of tissue extracts


Evolution of the CRISPR-Cas adaptive immunity systems in prokaryotes: models and observations on virus–host coevolution
Eugene V. Koonin and Yuri I. Wolf
DOI: 10.1039/C4MB00438H, Review Article

Evolution of the CRISPR-Cas adaptive immunity systems in prokaryotes


Clearance of the intracellular high level of the Tau protein directed by an artificial synthetic hydrolase
Ting-Ting Chu, Qian-Qian Li, Tian Qiu, Zhan-Yi Sun, Zhi-Wen Hu, Yong-Xiang Chen, Yu-Fen Zhao and Yan-Mei Li
DOI: 10.1039/C4MB00508B, Communication

Clearance of the intracellular high level of the Tau protein directed by an artificial synthetic hydrolase


CIP2A regulates cancer metabolism and CREB phosphorylation in non-small cell lung cancer
Bo Peng, Ningjing Lei, Yurong Chai, Edward K. L. Chan and Jian-Ying Zhang
DOI: 10.1039/C4MB00513A, Paper

CIP2A regulates cancer metabolism and CREB phosphorylation in non-small cell lung cancer


Molecular dynamics-based discovery of novel phosphodiesterase-9A inhibitors with non-pyrazolopyrimidinone scaffolds
Zhe Li, Xiao Lu, Ling-Jun Feng, Ying Gu, Xingshu Li, Yinuo Wu and Hai-Bin Luo
DOI: 10.1039/C4MB00389F, Paper

phosphodiesterase-9A inhibitors with non-pyrazolopyrimidinone scaffolds

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Recent HOT Molecular BioSystems articles

The following are HOT articles, as recommened by the reviewers of the articles. These have all been made free to access until 24th October:

Network pharmacology study on the mechanism of traditional Chinese medicine for upper respiratory tract infection
Xinzhuang Zhang, Jiangyong Gu, Liang Cao, Na Li, Yiming Ma, Zhenzhen Su, Gang Ding, Lirong Chen, Xiaojie Xu and Wei Xiao
Mol. BioSyst., DOI: 10.1039/C4MB00164H, Paper


Vitreous proteomic analysis of idiopathic epiretinal membranes
Jing Yu, Le Feng, Yan Wu, Hao Wang, Jun Ba, Wei Zhu and Chunlei Xie
Mol. BioSyst., DOI: 10.1039/C4MB00240G, Paper


Effect of a Ru(II) polypyridyl complex [Ru(bpy)2(mdpz)]2+ on the stabilization of the RNA triplex poly(U)·poly(A)*poly(U)
Xiaojun He, Jia Li, Hong Zhang and Lifeng Tan
Mol. BioSyst., DOI: 10.1039/C4MB00304G, Paper


Informative Bayesian Model Selection: a method for identifying interactions in genome-wide data
Mehran Aflakparast, Ali Masoudi-Nejad, Joseph H . Bozorgmehr and Shyam Visweswaran
Mol. BioSyst., DOI: 10.1039/C4MB00123K, Paper


Prioritizing candidate disease miRNAs by integrating phenotype associations of multiple diseases with matched miRNA and mRNA expression profiles
Chaohan Xu, Yanyan Ping, Xiang Li, Hongying Zhao, Li Wang, Huihui Fan, Yun Xiao and Xia Li
Mol. BioSyst., DOI: 10.1039/C4MB00353E, Method


Molecular docking and molecular dynamics studies on the structure–activity relationship of fluoroquinolone for the HERG channel
Fang Luo, Jiangyong Gu, Lirong Chen and Xiaojie Xu
Mol. BioSyst., DOI: 10.1039/C4MB00396A, Paper


Dynamic changes in metabolic profiles of rats subchronically exposed to mequindox
Limiao Jiang, Xiuju Zhao, Chongyang Huang, Hehua Lei, Huiru Tang and Yulan Wang
Mol. BioSyst., DOI: 10.1039/C4MB00218K, Paper


Concerted bioinformatic analysis of the genome-scale blood transcription factor compendium reveals new control mechanisms
Anagha Joshi and Berthold Gottgens
Mol. BioSyst., DOI: 10.1039/C4MB00354C, Paper


A multi-omics strategy resolves the elusive nature of alkaloids in Podophyllum species
Joaquim V. Marques, Doralyn S. Dalisay, Hong Yang, Choonseok Lee, Laurence B. Davin and Norman G. Lewis
Mol. BioSyst., DOI: 10.1039/C4MB00403E, Paper

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Recent HOT Molecular BioSystems articles

FMRP regulates miR196a-mediated repression of HOXB8 via interaction with the AGO2 MID domain
Ying Li, Wei Tang, Li-rong Zhang and Chun-yang Zhang
Mol. BioSyst., 2014,10, 1757-1764
DOI: 10.1039/C4MB00066H

Graphical abstract

Free to access until 4th July 2014


Discovery of protein–RNA networks
Davide Cirillo, Carmen Maria Livi, Federico Agostini and Gian Gaetano Tartaglia
Mol. BioSyst., 2014,10, 1632-1642
DOI: 10.1039/C4MB00099D

Graphical abstract

Free to access until 4th July 2014


Systems pharmacology strategies for anticancer drug discovery based on natural products
Fang Luo, Jiangyong Gu, Lirong Chen and Xiaojie Xu
Mol. BioSyst., 2014,10, 1912-1917
DOI: 10.1039/C4MB00105B

Graphical abstract

Free to access until 4th July 2014

 


 

The metabolic impact of methamphetamine on the systemic metabolism of rats and potential markers of methamphetamine abuse
Tian Zheng, Linsheng Liu, Jian Shi, Xiaoyi Yu, Wenjing Xiao, Runbing Sun, Yahong Zhou, Jiye Aa and Guangji Wang
Mol. BioSyst., 2014,10, 1968-1977
DOI: 10.1039/C4MB00158C

Graphical abstract

Free to access until 4th July 2014


Experimental design, validation and computational modeling uncover DNA damage sensing by DNA-PK and ATM
R. J. Flassig, G. Maubach, C. Täger, K. Sundmacher and M. Naumann
Mol. BioSyst., 2014,10, 1978-1986
DOI: 10.1039/C4MB00093E

Graphical abstract

Free to access until 4th July 2014 

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Recent HOT Molecular BioSystems articles

Understanding and applying tyrosine biochemical diversity
Lyn H. Jones, Arjun Narayanan and Erik C. Hett
Mol. BioSyst., 2014,10, 952-969
DOI: 10.1039/C4MB00018H

Understanding and applying tyrosine biochemical diversity

Free to access until 7th May 2014


Cell growth and protein expression of Shewanella oneidensis in biofilms and hydrogel-entrapped cultures
Yingdan Zhang, Chun Kiat Ng, Yehuda Cohen and Bin Cao
Mol. BioSyst., 2014,10, 1035-1042
DOI: 10.1039/C3MB70520J

Cell growth and protein expression of Shewanella oneidensis in biofilms and hydrogel-entrapped cultures

Free to access until 7th May 2014


Quantitative phosphoproteomic profiling of PINK1-deficient cells identifies phosphorylation changes in nuclear proteins
Xiaoyan Qin, Chaoya Zheng, John R. Yates III and Lujian Liao
Mol. BioSyst., 2014, Advance Article
DOI: 10.1039/C3MB70565J

Quantitative phosphoproteomic profiling of PINK1-deficient cells identifies phosphorylation changes in nuclear proteins

Free to access until 7th May 2014


Regulation of cell survival by the HIP-55 signaling network
Chengzhi Yang, Zenggang Li, Zhi Shi, Kangmin He, Aiju Tian, Jimin Wu, Youyi Zhang and Zijian Li
Mol. BioSyst., 2014, Advance Article
DOI: 10.1039/C3MB70552H

Regulation of cell survival by the HIP-55 signaling network

Free to access until 7th May 2014


Prioritization of candidate disease genes by enlarging the seed set and fusing information of the network topology and gene expression
Shao-Wu Zhang, Dong-Dong Shao, Song-Yao Zhang and Yi-Bin Wang
Mol. BioSyst., 2014, Advance Article
DOI: 10.1039/C3MB70588A

Prioritization of candidate disease genes by enlarging the seed set and fusing information of the network topology and gene expression

 

Free to access until 7th May 2014

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Free access to HOT articles

These HOT articles were recommended by our referees and are free to access for 4 weeks*

A novel network pharmacology approach to analyse traditional herbal formulae: the Liu-Wei-Di-Huang pill as a case study
Xujun Liang, Huiying Li and Shao Li 
Mol. BioSyst., 2014, Advance Article
DOI: 10.1039/C3MB70507B, Paper

Graphical abstract: A novel network pharmacology approach to analyse traditional herbal formulae: the Liu-Wei-Di-Huang pill as a case study

A comprehensive analysis of the Streptococcus pyogenes and human plasma protein interaction network
Kristoffer Sjöholm, Christofer Karlsson, Adam Linder and Johan Malmström 
Mol. BioSyst., 2014, Advance Article
DOI: 10.1039/C3MB70555B, Paper

Graphical abstract: A comprehensive analysis of the Streptococcus pyogenes and human plasma protein interaction network

Engineering reduced evolutionary potential for synthetic biology
Brian A. Renda, Michael J. Hammerling and Jeffrey E. Barrick 
Mol. BioSyst., 2014, Advance Article
DOI: 10.1039/C3MB70606K, Review Article

Graphical abstract: Engineering reduced evolutionary potential for synthetic biology

Structure-based engineering and comparison of novel split inteins for protein ligation
A. Sesilja Aranko, Jesper S. Oeemig, Dongwen Zhou, Tommi Kajander, Alexander Wlodawer and Hideo Iwaï 
Mol. BioSyst., 2014, Advance Article
DOI: 10.1039/C4MB00021H, Paper

Graphical abstract: Structure-based engineering and comparison of novel split inteins for protein ligation
*Free access to individuals is provided through an RSC Publishing personal account. It’s quick, easy and more importantly – free – to register!

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