Free to access HOT articles!

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

Large-scale cytological profiling for functional analysis of bioactive compounds
Marcos H. Woehrmann, Walter M. Bray, James K. Durbin, Sean C. Nisam, Alicia K. Michael, Emerson Glassey,  Joshua M. Stuart  and R. Scott Lokey  
DOI: 10.1039/C3MB70245F

Activation mechanism of claudin-4 by ephrin type-A receptor 2: a molecular dynamics approach
V. Bhavaniprasad, J. Febin Prabhu Dassa and S. Jayanthi  
DOI: 10.1039/C3MB70271E

Role of feedback and network architecture in controlling virulence gene expression in Bordetella
Mahendra Kumar Prajapata and Supreet Saini  
DOI: 10.1039/C3MB70213H

A fluorogenic probe for β-galactosidase activity imaging in living cells
Junyan Han, Myung Shin Han and Ching-Hsuan Tung  
DOI: 10.1039/C3MB70269C

The association of the cytoplasmic domains of interleukin 4 receptor alpha and interleukin 13 receptor alpha 2 regulates interleukin 4 signaling
Allison-Lynn Andrews, Ida Karin Nordgren, Gemma Campbell-Harding, John W. Holloway, Stephen T. Holgate, Donna E. Davies and Ali Tavassoli  
DOI: 10.1039/C3MB70298G

Network-based analysis of omics with multi-objective optimization
Ettore Mosca  and Luciano Milanesi  
DOI: 10.1039/C3MB70327D

Activity-based protein profiling of secreted cellulolytic enzyme activity dynamics in Trichoderma reesei QM6a, NG14, and RUT-C30
Lindsey N. Anderson, David E. Culley, Beth A. Hofstad, Lacie M. Chauvigné-Hines, Erika M. Zink, Samuel O. Purvine,   Richard D. Smith, Stephen J. Callister,  Jon M. Magnuson and Aaron T. Wright 
DOI: 10.1039/C3MB70333A

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Theoretical study of LIM kinase yields new inhibitors for potential cancer therapies

Published on behalf of Kelly E. Theisen, web-writer for Molecular BioSystems.

Hou et al. at Soochow and Zhejiang Universities in China have used various computational methods to find new inhibitors for LIM kinase 2. They have also used the same methods to evaluate the effectiveness of many existing inhibitors which have been studied experimentally, to understand why certain inhibitors might be more potent than others. Hou’s recent paper1 featured on the cover of Molecular Biosystems, Issue 10.

 

LIM kinases (LIMKs) have been found to be highly expressed in many types of tumors, and regulate several proteins crucial for cell division. Inhibitors of these kinases would therefore make possible avenues for cancer therapies. Most current inhibitors target LIMK1, one of the two isoforms that make up the LIMK family, but there is a need for improved inhibitors for LIMK2, the other isoform, and the focus of the current study.

Little research has been done on LIMK2 previously, as there is no crystal structure available in the Protein Data Bank (PDB), a requirement for theoretical models. In order to overcome this obstacle, Hour et al used homology modeling with LIMK1 to obtain a structure for LIMK2. This process used the sequence of LIMK2, and the known crystal structure of LIMK1 to produce a LIMK2 structure by established modeling programs. Due to the high level of sequence similarity (~60%), the structures for LIMK1 and LIMK2 are likely to be very similar as well. After a structure was obtained, small inhibitor molecules from an experimental study could be docked to LIMK2 and analysed computationally.

The researchers found that the flexibility of the binding site itself is extremely important for inhibitor recognition, as determined by analyzing the conformations of amino acids at the binding site before and after binding occurred. This flexibility would allow LIMK2 to bind many types and sizes of inhibitors, as observed experimentally. Additionally, the nonpolar interactions (van der Waals forces) at the binding site account for the majority of the binding energy, and can be correlated with the binding affinity of an inhibitor.

Schematic representation of interactions between a designed LIMK2 inhibitor and the modelled LIMK2

Most significantly, the researchers were able to design and test four new inhibitors based on the criteria for ideal binding affinity. These designed inhibitors have two sides connected by a linker (type II inhibitors). One side will bind to the substrate or allosteric site, while the other will bind to a nucleotide pocket, which are spatially close to each other on the surface of LIMK2. The inhibitors proposed by the researchers could later be tested experimentally, but the simulation results suggest that they will be as effective as those currently available, if not more effective.

  1. Theoretical study on the interaction of pyrrolopyrimidine derivatives as LIMK2 inhibitors:  insight into structure-based inhibitor design, Mingyun Shen, Shunye Zhou, Youyong Li, Dan Li and Tinguin Hou, Mol. BioSyst., 2013, 9, 2435-2446. DOI: 10.1039/C3MB70168A

If you would like to read more papers by Tingjun Hou et al, please click here!

Or for more MBS HOT papers, browse the blog.

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Free to access HOT articles!

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

An in silico exploration of the interaction mechanism of pyrazolo[1,5-a]pyrimidine type CDK2 inhibitors
Yan Li, Weimin Gao, Feng Li, Jinghui Wang, Jingxiao Zhang, Yinfeng Yang, Shuwei Zhang and Ling Yang  
DOI: 10.1039/C3MB70186G 

GA 

Theoretical study on the interaction of pyrrolopyrimidine derivatives as LIMK2 inhibitors: insight into structure-based inhibitor design
Mingyun Shen, Shunye Zhou, Youyong Li, Dan Li and Tingjun Hou
DOI: 10.1039/C3MB70168A

GA

Selective inhibition of the unfolded protein response: targeting catalytic sites for Schiff base modification
Susana M. Tomasio, Heather P. Harding, David Ron, Benedict C. S. Cross and Peter J. Bond 
DOI: 10.1039/C3MB70234K

GA

The three-dimensional context of a double helix determines the fluorescence of the internucleoside-tethered pair of fluorophores
Valeri Metelev, Surong Zhang, David Tabatadze, Anand T. N. Kumar and Alexei Bogdanov
DOI: 10.1039/C3MB70108E

GA 

BH3 helix-derived biophotonic nanoswitches regulate cytochrome c release in permeabilised cells
Robert J. Mart, Rachel J. Errington, Catherine L. Watkins, Sally C. Chappell, Marie Wiltshire, Arwyn T. Jones, Paul J. Smith and Rudolf K. Allemann  
DOI: 10.1039/C3MB70246D

GA

Metabolomic identification of diagnostic plasma biomarkers in humans with chronic heart failure

Juan Wang, Zhongfeng Li, Jianxin Chen, Huihui Zhao, Liangtao Luo, Chan Chen, Xuegong Xu, Wenting Zhang, Kuo Gao, Bin Li, Junpeng Zhang and Wei Wang
DOI: 10.1039/C3MB70227H

GA

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Molecular Biosystems: The Most Cited Articles of 2010 and 2011

The editors here at MBS want to highlight the Journal’s most cited articles of 2010 and 2011, and to take the opportunity to showcase some of the fantastic work that our authors have produced over the last two years. Congratulations to everyone!

As of now, all of the below articles will be free for 4 weeks (until Monday 16th Sept),* so make the most of this opportunity to download the full papers!

Top 3 Cited Reviews:

  1. LF Peng et. al.: Small-molecule modulators of the Sonic Hedgehog signaling pathway (DOI: 10.1039/b910196a).

    A review on our current understanding of small-molecule modulators of Sonic hedgehog (Shh) signalling, and at which points in the pathway modulators are active. Peng and colleagues go on to include discussion of modulator application in therapeutics and our current understanding of this phenomenon.


  2. V Torchilin et. al.: Intracellular transduction using cell-penetrating peptides  (DOI: 10.1039/b916297f).

    A review highlighting the mechanisms of cell penetrating peptide (CPP)-mediated deliver of various agents, including peptides, proteins and small molecules. Torchilin and colleagues go on to provide excellent examples to illustrate the potential use of CPPs in biology and medicine.


  3. SJ Baserja: When ribosomes go bad: diseases of ribosome biogenesis (DOI: 10.1039/b919670f).

    A review highlighting diseases of ribosome biogenesis, a biological error which was, until recently, assumes to be lethal. Baserga and colleagues discuss our limitations in understanding the molecular mechanisms underlying these diseases.


Top 10 Cited Research Papers:

  1. XA Xiao et. al.: GPCR-2L: predicting G protein-coupled receptors and their types by hybridizing two different modes of pseudo amino acid compositions (DOI: 10.1039/c0mb00170h).

    Xiao and colleagues develop a new predictor for G-protein coupled receptors (GPCRs) by hybridising two different modes of pseudo-amino acid composition. Their predictor displays high success rates and has potential application in drug development.


  2. XA Xiao et. al.: iLoc-Plant: a multi-label classifier for predicting the subcellular localization of plant proteins with both single and multiple sites (DOI: 10.1039/c1mb05232b).

    Xiao and colleagues develop a new predictor for the sub-cellular localisation of plant proteins, which introduces ‘multi-labeled learning’, allowing for the detection of multiple-location proteins.


  3. SC Connor et. al.: Integration of metabolomics and transcriptomics data to aid biomarker discovery in type 2 diabetes (DOI: 10.1039/b914182k).

    A paper on non-targeted metabolomics technologies and their use in providing novel biomarkers of disease and drug efficacy. Combined analysis of analysis of metabolite and gene expression changes revealed 24 distinct pathways that were altered in the diabetic model.


  4. A Salvati et. al.: Time and space resolved uptake study of silica nanoparticles by human cells (DOI: 10.1039/c0mb00109k)

  5. JS Hartig et. al.: A ligand-dependent hammerhead ribozyme switch for controlling mammalian gene expression (DOI: 10.1039/b923076a)

  6. CJ Schofield et. al.: A miniaturized screen for inhibitors of Jumonji histone demethylases (DOI: 10.1039/b912993f)

  7. BF Cravatt et. al.: Characterization of mice lacking candidate N-acyl ethanolamine biosynthetic enzymes provides evidence for multiple pathways that contribute to endocannabinoid production in vivo (DOI: 10.1039/c000237b)

  8. TDH Bugg et. al.: Development of novel assays for lignin degradation: comparative analysis of bacterial and fungal lignin degraders (DOI: 10.1039/b908966g)

  9. JB Bramsden et. al.: Utilization of unlocked nucleic acid (UNA) to enhance siRNA performance in vitro and in vivo (DOI: 10.1039/b918869j)

  10. SS Sidhu et. al.: Coevolution of PDZ domain-ligand interactions analyzed by high-throughput phage display and deep sequencing (DOI: 10.1039/c0mb00061b)

   

*free through an RSC account

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Free to access HOT articles!

 These articles are HOT as recommended by the referees. And we’ve made them free to access for 4 weeks*

Exploring higher-order EGFR oligomerisation and phosphorylation—a combined experimental and theoretical approach
Noga Kozer, Dipak Barua, Suzanne Orchard, Eduoard C. Nice, Antony W. Burgess, William S. Hlavacek and Andrew H. A. Clayton 
DOI: 10.1039/C3MB70073A


Human cathelicidin peptide LL37 binds telomeric G-quadruplex
Jagannath Jana, Rajiv Kumar Kar, Anirban Ghosh, Atanu Biswas, Surajit Ghosh, Anirban Bhunia and Subhrangsu Chatterjee 
DOI: 10.1039/C3MB70030E


 

Urea in aqueous solution studied by quantum mechanical charge field-molecular dynamics (QMCF-MD)
Alexander K. H. Weiss and Thomas S. Hofer
DOI: 10.1039/C3MB25522K


Functional specific roles of FADD: comparative proteomic analyses from knockout cell lines
Hongqin Zhuang, Ziyi Gan, Weiwei Jiang, Xiangyu Zhang and Zi-Chun Hua
DOI: 10.1039/C3MB70023B


Extolling the benefits of molecular therapeutic lipidation
Miriam Avadisian and Patrick T. Gunning  
DOI: 10.1039/C3MB70147F


Genomics and proteomics in solving brain complexity
Beena M. Kadakkuzha and Sathyanarayanan V. Puthanveettil  
DOI: 10.1039/C3MB25391K

*Free access to individuals is provided through an RSC Publishing personal account. Registration is quick, free and simple

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Final chance to register for ISACS11 – don’t miss Shokat, Trauner, Yonath and many more!

Registration Deadline – Friday 21 June 2013

 

You have just a few days left to secure your place at the 11th conference in the International Symposia on Advancing the Chemical Sciences (ISACS) series as registration for Challenges in Chemical Biology (ISACS11) closes on Friday 21 June 2013.

Don’t miss your opportunity to join outstanding researchers from across the globe to explore the themes of immunology, microbiology, chromatin biology, epigenetics, cancer biology, systems biology and neuroscience.

Registration is quick and simple via the online booking system and spaces are filling up fast so be sure to guarantee yours now.

Programme Live

We are pleased to announce that the ISACS11 programme is now available to view online. Take a look at the schedule to discover the full speaker line up and stimulating lecture titles over the entire four days.

Find Out More

For the latest information on Challenges in Chemical Biology (ISACS11) or any of the conferences in the series, please sign up for the exclusive newsletter, follow ISACS on twitter or visit the dedicated webpage.

I look forward to welcoming you to Boston.

Best regards

Professor Ben Davis
Chairman of the Conference Committee
isacs@rsc.org

The International Symposia on Advancing the Chemical Sciences (ISACS) partner the RSC’s flagship journal Chemical Science – Winner of the ALPSP Award for Best New Journal 2011.

                    

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Take 1.. minute for chemistry in health

Do you know how chemical scientists can tackle global challenges in Human Health? If so, the RSC is running a one minute video competition this summer for young researchers such as PhD and Post-doc students; get involved and innovate the way scientists share their research. Your video should communicate your own personal research or an area of research that interests you, highlighting its significance and impact to Human Health.

Five videos will be shortlisted by our judging panel and the winner will be selected during the ‘How does chemistry keep us healthy?’ themed National Chemistry Week taking place 16-23 November. 

A £500 prize and a fantastic opportunity to shadow the award winning video Journalist, Brady Harran, is up for grabs for the winner.

The judging panel will include the makers of The Periodic Tale of Videos, Martyn Poliakoff and Brady Harran, and RSC Division representatives.

Check out our webpage for further details of the competition and an example video. 

The competition will open 02 April 2013 and the closing date for entries is 01 July 2013. Please submit your entries to rsc.li/take-1-video-competition.

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Challenges in Chemical Biology (ISACS11)

Early Bird Deadline – 31 May 2013

Early bird registration for Challenges in Chemical Biology (ISACS11) closes on Friday. Make sure you register for this significant conference before 31 May 2013 to guarantee your place at the reduced fee.

For full details including themes and speaker details, please visit the dedicated website.

Challenges in Chemical Biology will be the second event in the International Symposia on Advancing the Chemical Sciences (ISACS) series in 2013. Building upon the success of ISACS 5: Challenges in Chemical Biology, which took place in 2011, the meeting will bring together leading scientists from across the world to discuss the latest applications of chemical tools and techniques for probing biological problems.

The conference will take place at Massachusetts Institute of Technology and the Scientific Committee warmly invites you to take part in ISACS 11 and looks forward to welcoming you to Boston.

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Free to access HOT articles in May

 These articles are HOT as recommended by the referees. And we’ve made them free to access for 4 weeks*.

Identifying subcellular localizations of mammalian protein complexes based on graph theory with a random forest algorithm
Zhan-Chao Li, Yan-Hua Lai, Li-Li Chen, Chao Chen, Yun Xie, Zong Dai and Xiao-Yong Zou 
DOI: 10.1039/C3MB25451H


Quantifying the similarity of monotonic trajectories in rough and smooth fitness landscapes
Alexander E. Lobkovsky, Yuri I. Wolf and Eugene V. Koonin 
DOI: 10.1039/C3MB25553K

 


A study of Caenorhabditis elegans DAF-2 mutants by metabolomics and differential correlation networks
Cecilia Castro, Jan Krumsiek, Nicolas J. Lehrbach, Steven A. Murfitt, Eric A. Miska and Julian L. Griffin
DOI: 10.1039/C3MB25539E


A comprehensive analysis of the influence of drug binding kinetics on drug action at molecular and systems levels
Ning Yin, Jianfeng Pei and Luhua Lai
DOI: 10.1039/C3MB25471B

 


DNA thermodynamic stability and supercoil dynamics determine the gene expression program during the bacterial growth cycle
Patrick Sobetzko, Monika Glinkowska, Andrew Travers and Georgi Muskhelishvili 
DOI: 10.1039/C3MB25515H

 


Proteomic and ionomic profiling reveals significant alterations of protein expression and calcium homeostasis in cystic fibrosis cells
Domenico Ciavardelli, Melania D’Orazio, Luisa Pieroni, Ada Consalvo, Claudia Rossi, Paolo Sacchetta, Carmine Di Ilio, Andrea Battistoni and Andrea Urbani 
DOI: 10.1039/C3MB25594H

 


Mechanism of action-based classification of antibiotics using high-content bacterial image analysis
Kelly C. Peach, Walter M. Bray, Dustin Winslow, Peter F. Linington and Roger G. Linington 
DOI: 10.1039/C3MB70027E

 

 

*Free access to individuals is provided through an RSC Publishing personal account. Registration is quick, free and simple

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HOT Comm: Visual genomic DNA detection without PCR

A group from the National University of Singapore and DSO National Laboratories, Singapore led by Mahesh Uttamchandani use gold nanoparticles to detect DNA sequences without the use of PCR.

PCR is normally needed to amplify the quantity of natural DNA samples for visual detection before they can be detected. For point-of-care applications in particular, the need for a PCR machine is cumbersome. In this communication, the researchers demonstrate a method for specific visual detection of a DNA sample without the need for PCR.

Gold nanoparticles are often coated with ligands for target specific detection. The different inter-particle distances provide a visual output when the target is added. Well-dispersed gold nanoparticles appear read and as the distance decreases this colour changes down the spectrum to purple and then to blue. Aggregation of the nanoparticles causes them to precipitate as black or grey sediments. It has been shown before that synthetic DNA sequences can be detected in this way using thiolated ligands. This study uses double stranded DNA samples at room temperature – surprising as single stranded DNA is optimal for adsorbing to the gold nanoparticle surface.

The researchers test their simple assay on genomic DNA extracts from Salmonella enterica. The sensitivity of the system leaves much to be desired compared to when PCR is used, however this easy protocol at room temperature with readily available agents and no need for electricity has some great advantages. The lack of PCR in detection of genomic DNA is a positive step forward for point-of-care diagnostics.

This short and urgent Communication is now free to access for the next four weeks*:

Direct visual detection of Salmonella genomic DNA using gold nanoparticles
Kamaladasan Kalidasan, Jia Ling Neo and Mahesh Uttamchandani
DOI: 10.1039/C3MB25527A

*Free access to individuals is provided through an RSC Publishing personal account. Registration is quick, free and simple

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