Topology independent comparison of RNA 3D structures using the CLICK algorithm

RNA molecules are attractive therapeutic targets because non-coding RNA molecules have increasingly been found to play key regulatory roles in the cell. Comparing and classifying RNA 3D structures yields unique insights into RNA evolution and function. With the rapid increase in the number of atomic-resolution RNA structures, it is crucial to have effective tools to classify RNA structures and to investigate them for structural similarities at different resolutions.

type: 
Journal Paper
journal: 
Nuclei Acids Research 2016, doi: 10.1093/nar/gkw819
pubmed: 
27634929
Url: 
http://nar.oxfordjournals.org/content/early/2016/09/14/nar.gkw819.abstract?keytype=ref&ijkey=WsEFoSR4nWzxvyH
Impact Factor: 
6.03
Date of acceptance: 
2016-09-14

Weibel-Palade body size modulates the adhesive activity of its von Willebrand Factor cargo in cultured endothelial cells

Changes in the size of cellular organelles are often linked to modifications in their function. Endothelial cells store von Willebrand Factor (vWF), a glycoprotein essential to haemostasis in Weibel-Palade bodies (WPBs), cigar-shaped secretory granules that are generated in a wide range of sizes. We recently showed that forcing changes in the size of WPBs modifies the activity of this cargo. We now find that endothelial cells treated with statins produce shorter WPBs and that the vWF they release at exocytosis displays a reduced capability to recruit platelets to the endothelial cell surface.

type: 
Journal Paper
journal: 
Scientific Reports 6, Article no. 32473 (2016), doi:10.1038/srep32473
Url: 
http://www.nature.com/articles/srep32473
Impact Factor: 
5.228
Date of acceptance: 
2016-08-09

Benzene Probes in Molecular Dynamics Simulations Reveal Novel Binding Sites for Ligand Design

Protein flexibility poses a major challenge in binding site identification. Several computational pocket detection methods that utilize small-molecule probes in molecular dynamics (MD) simulations have been developed to address this issue. Although they have proven hugely successful at reproducing experimental structural data, their ability to predict new binding sites that are yet to be identified and characterized has not been demonstrated.

type: 
Journal Paper
journal: 
Journal of Physical Chemistry, 2016, 7, Pg 3452-3457, doi: 10.1021/acs.jpclett.6b01525
pubmed: 
27532490
Url: 
http://www.ncbi.nlm.nih.gov/pubmed/27532490
Impact Factor: 
8.539
Date of acceptance: 
2016-08-17

The severity of hereditary porphyria is modulated by the porphyrin exporter and Lan antigen ABCB6

Hereditary porphyrias are caused by mutations in genes that encode haem biosynthetic enzymes with resultant buildup of cytotoxic metabolic porphyrin intermediates. A longstanding open question is why the same causal porphyria mutations exhibit widely variable penetrance and expressivity in different individuals. Here we show that severely affected porphyria patients harbour variant alleles in the ABCB6 gene, also known as Lan, which encodes an ATP-binding cassette (ABC) transporter. Plasma membrane ABCB6 exports a variety of disease-related porphyrins.

type: 
Journal Paper
journal: 
Nature Communications 7, 2016, Article no: 12353, doi:10.1038/ncomms12353
Url: 
http://www.nature.com/ncomms/2016/160810/ncomms12353/full/ncomms12353.html
Impact Factor: 
11.05
Date of acceptance: 
2016-06-23

APD Colony Counter App: Using Watershed Algorithm for improved colony counting

The counting of colonies to quantitate bacteria is an important process in labs for research, clinical diagnosis, and environmental monitoring e.g. in water. Generally counted manually, progress in technology has automated the process through colony counters that can be purchased but can be costly. While efficient, there remains also a challenge correctly detecting clustered colonies compromising inaccurate counts. Leveraging on the smartphone camera, we developed an app that processes images of colony plates and automatically counts them.

type: 
Journal Paper
journal: 
Nature Methods Application Notes 2016
Url: 
http://www.nature.com/app_notes/nmeth/index.html
Impact Factor: 
32.072
Date of acceptance: 
2016-08-11

Tertiary Element Interaction in HIV-1 TAR

HIV-1 replication requires binding to occur between Trans-activation Response Element (TAR) RNA and the TAT protein. This TAR-TAT binding depends on the conformation of TAR, and therapeutic development has attempted to exploit this dynamic behavior. Here we simulate TAR dynamics in the context of mutations inhibiting TAR binding. We find that two tertiary elements, the apical loop and the bulge, can interact directly, and this interaction may be linked to the affinity of TAR for TAT.

type: 
Journal Paper
journal: 
Journal of Chemical Information and Modeling, 2016, doi: 10.1021/acs.jcim.6b00152
Url: 
http://pubs.acs.org/doi/abs/10.1021/acs.jcim.6b00152
Impact Factor: 
2.88

The Multifaceted Roles of Molecular Dynamics Simulations in Drug Discovery

Discovery of new therapeutics is a very challenging, expensive and time-consuming process. With the number of approved drugs declining steadily, combined with increasing costs, a rational approach is needed to facilitate, expedite and streamline the drug discovery process. In silico methods are playing key roles in the discovery of a growing number of marketed drugs. The use of computational approaches, particularly molecular dynamics, in drug design is rapidly gaining momentum and acceptance as an essential part of the toolkit for modern drug discovery.

type: 
Journal Paper
journal: 
Current Pharmaceutical Design, Vol. 22, Issue 23, 2016, Pg. 3585-3600, doi: 10.2174/1381612822666160425120507
pubmed: 
27108593
Url: 
http://www.eurekaselect.com/141460/article#
Impact Factor: 
3.052
Date of acceptance: 
2016-04-22

PP2ACdc55’s role in reductional chromosome segregation during achiasmate meiosis in budding yeast is independent of its FEAR function

PP2ACdc55 is a highly conserved serine-threonine protein phosphatase that is involved in diverse cellular processes. In budding yeast, meiotic cells lacking PP2ACdc55 activity undergo a premature exit from meiosis I which results in a failure to form bipolar spindles and divide nuclei. This defect is largely due to its role in negatively regulating the Cdc Fourteen Early Anaphase Release (FEAR) pathway. PP2ACdc55 prevents nucleolar release of the Cdk (Cyclin-dependent kinase)-antagonising phosphatase Cdc14 by counteracting phosphorylation of the nucleolar protein Net1 by Cdk.

type: 
Journal Paper
journal: 
Scientific Reports 2016, 6:30397, DOI: 10.1038/srep30397
Url: 
http://www.nature.com/articles/srep30397
Impact Factor: 
5.228
Date of acceptance: 
2016-06-30

Reactivation of mutant p53: Constraints on mechanism highlighted by principal component analysis of the DNA binding domain

Most p53 mutations associated with cancer are located in its DNA binding domain (DBD). Many structures (X-ray and NMR) of this domain are available in the protein data bank (PDB) and a vast conformational heterogeneity characterizes the various free and complexed states. The major difference between the apo and the holo-complexed states appears to lie in the L1 loop. In particular, the conformations of this loop appear to depend intimately on the sequence of DNA to which it binds.

type: 
Journal Paper
journal: 
Proteins: Structure, Function, and Bioinformatics, 18 Jun 2016, doi: 10.1002/prot.25089
pubmed: 
27317883
Url: 
http://www.ncbi.nlm.nih.gov/pubmed/27317883
Impact Factor: 
2.499

PDK1-SGK1 signaling sustains AKT-independent mTORC1 activation and confers resistance to PI3Kα inhibition

PIK3CA, which encodes the p110α subunit of PI3K, is frequently mutated and oncogenic in breast cancer. PI3Kα inhibitors are in clinical development and despite promising early clinical activity, intrinsic resistance is frequent among patients. We have previously reported that residual downstream mTORC1 activity upon treatment with PI3Kα inhibitors drives resistance to these agents. However, the mechanism underlying this phenotype is not fully understood. Here we show that in cancer cells resistant to PI3Kα inhibition, PDK1 blockade restores sensitivity to these therapies.

type: 
Journal Paper
journal: 
Cancer Cell 2016 Aug 8;30(2):229-242. doi: 10.1016/j.ccell.2016.06.004
pubmed: 
27451907
Url: 
http://www.ncbi.nlm.nih.gov/pubmed/27451907
Impact Factor: 
12.02
Date of acceptance: 
2016-06-09
Syndicate content