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Change the wsdl path and the function call. Hope this saves some time for someone!
Applied Bimatics - An Informatics Blog
I am a clinician with a passion for informatics. This blog is about my medical / health / bio INFORMATICS experiments in a clinical context.
The information presented here is not intended to diagnose, treat, cure or prevent any disease. Always seek the advice of your own physician or other qualified health care professional. Read full Disclaimer.
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Monday, April 22, 2013
Change the wsdl path and the function call. Hope this saves some time for someone!
Friday, April 19, 2013
The great anti-ageing mantra
Matrix metalloproteinases (MMPs) are important in dermatology as they are involved in remodelling extracellular matrix (ECM). It is a big family of enzymes, all having a common domain structure with a pro-peptide region, catalytic domain, hinge region and the haemopexin-like C-terminal domain. They are involved in a variety of biological functions. MMP1 is involved in the premature ageing in smokers. Inhibition of certain MMPs have anti-ageing effect while inhibition of others promote hyperproliferative disorders and scars. However because of the structural similarities, rational design of specific inhibitors are very difficult. Most of the rationally designed MMP inhibitors like marimastat (BB-2516) and cipemastat (Ro 32-3555) have performed poorly in clinical studies.
1. Lahmann, Christine et al. "Matrix metalloproteinase-1 and skin ageing in smokers." The Lancet 357.9260 (2001): 935-936.
2. Udi, Yael et al. "Unraveling hidden regulatory sites in structurally homologous metalloproteases." Journal of Molecular Biology (2013).
Monday, April 01, 2013
Rational Peptide Design
A hexapeptide mimic of the N-terminal end of SNAP-25 which competes with this protein for a position in the SNARE complex is being used as a cosmetic peptide to eliminate facial lines resulting from muscular activity. However industry standard for the same indication is Botulinum Neurotoxin A that can enter the neuron by SV2 mediated endocytosis. It is not known whether the hexapeptide mimic actually enters the neuron in sufficient concentration to give the proposed effect. Read the clinical implications of the story here.
One of the earliest studies on this Acetyl Hexapeptide - 3 gives a ‘rational’ explanation for this limitation. Let me quote from the article:
Sequence and structure analysis of the N-terminal of SNAP-25 revealed the sequence EMQRR that display a high propensity to acquire an alpha-helical Structure along with a pronounced coiled-coil probability. AGADIR, a programme that estimates helical propensity of peptides, predicted a remarkable 12 % probability for this small peptide. These properties suggest that a peptide patterned after this sequence may modulate Calcium dependent exocytosis, Similar to those peptides derived from the C-terminal of SNAP-25.
I have the following questions about the rational explanation:
1. How can a hexapeptide have coiled-coil probability? (A minimum of 20 amino acids are needed for a coiled coil)
2. Is 12% probability remarkable?
3. How is a N-terminal mimic be similar to a C-terminal mimic?
Is this an attempt to suggest that the structural peculiarities mediate an HIV virus like receptor mediated endocytosis. If only we knew the truth. If only....
1. Blanes‐Mira, C et al. "A synthetic hexapeptide (Argireline) with antiwrinkle activity." International journal of cosmetic science 24.5 (2002): 303-310.
2. Rose, A. "Genome-Wide Identification of Arabidopsis Coiled-Coil Proteins and ..." 2004. <http://www.ncbi.nlm.nih.gov/pmc/articles/PMC389916/>
Monday, March 25, 2013
Best peptides for women
In continuation with my previous posts here and in skin deep, let me add few more things I found recently.
OK, now I am going to do something here that I rarely ever do on my blogs: I am going to shamelessly self promote me without actually giving away much information. My plan is to get noticed by the cosmetic tycoons and make some money out of this incessant babbling about beauty peptides :-)
The most commonly occurring tetra peptide in collagen is in fact GXXG and PXXP the commonest being GPPG.
The commonest tetra peptide repeats were GERG, GEKG, GFPG, GENG, GPRG, GHRG.
This is what terapeptide-21 is based on and there is nothing new till here.
But here comes the most surprising part!
The highest scoring short peptide of probable biological (signal) function does not belong to the above list!!
Hey, Do I hear my phone ringing?????
Friday, March 22, 2013
Beauty born out of Bioinformatics
The beauty and the anti-ageing industry is focused on finding ways to augment the fibrillar proteins collagen and elastin embedded in an extracellular matrix in the dermal layer of the skin. A pentapeptide KTTKS, within the carboxy terminal propeptide of type I collagen is extensively used as an anti-ageing cosmetic ingredient. The proposed mechanism of action is tricking the body into believing that there is excessive collagen degradation so that collagen biosynthetic pathway is stimulated. I have blogged about the potential limitations in Skin Deep .
Yet another peptide called tetrapeptide - 21 is claimed to be superior to KTTKS in anti-ageing properties. They claim to have discovered this by using bioinformatics methodology.
Let me quote from a product brochure:
We used bioinformatic methods to identify highly repetitive amino acid motifs in several human ECM proteins to identify sequences with inherent anti-aging activities. Using the amino acid sequences of collagen I, II, III, IV, V, elastin, and proelastin, tetra-peptide sequences were identified by their frequency of occurrence.
So dear biochemicians:
1. Where does the MMPs cleave collagen?
2. How many amino acid residues are there in collagen degradation fragments?
3. Do you think GXXG can mimick collagen fragment?
and dear bioinformaticians:
1. If we consider Collagen I & III into consideration (more relevant for skin) which are the commonest penta and hexa peptide motifs. Do they converge?
and finally dear cell biologists:
1. Do all collagen degradation fragments stimulate UVB induced hyaluronic acid degradation as described here: http://www.ncbi.nlm.nih.gov/pubmed/21454612
I have added a wiki page for this to summarise the findings. Feel free to add your thoughts here.
collagen alpha-1(I) chain preproprotein [Homo sapiens] : http://www.ncbi.nlm.nih.gov/protein/NP_000079.2
collagen alpha-2(I) chain precursor [Homo sapiens]
collagen alpha-1(III) chain preproprotein [Homo sapiens]
Monday, March 18, 2013
Importing ONTODerm Ontology
One of the problems they have encountered may be important to be addressed here. They could not import ONTODerm into Sesame. The URL provided in the ONTODerm home page is protege specific. However you can export the latest ONTODerm version in the native format from the project page on knoodl. Just request for a free membership to ONTODerm community.
Please keep me posted if you are using ONTODerm or DermKnowledgeBASE for any such projects and I wish both of them all the very best.
Monday, March 04, 2013
A Biochemical challenge!
I am back again with a challenge this time. My last challenge got excellent response and I finally published the findings here. This challenge is probably more to do with biochemistry and I hope the Biochemicians facebook group under Prof. PTS would find this problem interesting.
Before I define the problem, please read the posts here to know about the clinical context.
1. The Big Bang Theory
2. Beauty of dark hair.
In brief, Afamelanotide is a peptide drug being developed by Clinuvel pharmaceuticals for tanning. It is a synthetic alpha-MSH analog. (Click here for details)
A new patented molecule claims to have similar mechanism of action. (Click here for details)
The challenge is to find out:
1. How similar is the patented molecule to Afamelanotide?
2. Do you think the new molecule is designed for binding to cysteine rich keratin family in the hair cuticle? Can we improve this binding further by structural alterations?
3. Is the structure optimized for cutaneous penetration? In other words, what is the polarity and other relevant chemical and physical properties of the new molecule?
Please refer to the patented molecule as 'The bang' in your comments.
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