CASTP: protein surface computing server.
(NB: pockets prediction)
http://sts.bioengr.uic.edu/castp/calculation.php
Monday, April 12, 2010
Wednesday, March 31, 2010
Thursday, March 11, 2010
Monday, February 22, 2010
IAPP, pt 2.
Secondary structure, intrinsic disorders, proIAPP:
Amyloidogenic Propensity of ProIAPP and IAPP in the Presence of Negatively Charged Lipid Bilayers
Suman Jha
Biophysical Journal, Volume 96, Issue 3, Supplement 1, February 2009, Page 93a
(only abstract is free available)
Our CD studies show that the secondary structure content of ProIAPP and IAPP is predominantly unordered with small amounts of ordered secondary structure elements as confirmed by ATR-FTIR spectroscopy. However, in the presence of anionic membranes, ProIAPP forms predominantly α-helices and loops that subsequently transform to intermolecular β-sheet structures. For comparison, IAPP forms intermolecular β-sheets largely via unordered and loop structures.
The ATR-FTIR and fluorescence spectroscopy studies performed also reveal that ProIAPP has a higher amyloidogenic propensity in the presence of negatively charged membranes, but is still less amyloidogenic than IAPP.
Amyloidogenic Propensity of ProIAPP and IAPP in the Presence of Negatively Charged Lipid Bilayers
Suman Jha
Biophysical Journal, Volume 96, Issue 3, Supplement 1, February 2009, Page 93a
(only abstract is free available)
Our CD studies show that the secondary structure content of ProIAPP and IAPP is predominantly unordered with small amounts of ordered secondary structure elements as confirmed by ATR-FTIR spectroscopy. However, in the presence of anionic membranes, ProIAPP forms predominantly α-helices and loops that subsequently transform to intermolecular β-sheet structures. For comparison, IAPP forms intermolecular β-sheets largely via unordered and loop structures.
The ATR-FTIR and fluorescence spectroscopy studies performed also reveal that ProIAPP has a higher amyloidogenic propensity in the presence of negatively charged membranes, but is still less amyloidogenic than IAPP.
Amylin aka IAPP
On mechanism:
Intracellular amyloid-like deposits contain unprocessed pro-islet amyloid polypeptide (proIAPP) in beta cells of transgenic mice overexpressing the gene for human IAPP and transplanted human islets.
J. F. Paulsson . A. Andersson . P. Westermark .G. T. Westermark
Diabetologia (2006) 49: 1237–1246
http://www.springerlink.com/content/w824704516157312/fulltext.pdf
Fig. 8 Proposed sequence of events leading to islet amyloidosis.
a First, the processing of proIAPP is affected by factors such as high levels of NEFAs or glucose. Granules with amyloid-like fibres fuse and form an intracellular proIAPP amyloid-like deposit.
b Over time this aggregate enlarges and replaces most of the cell.
c This cell dies and the amyloid becomes extracellular and can act as a template for further amyloid formation.
d Amyloid is now made up by IAPP secreted from neighbouring beta cells. Formation of extracellular amyloid fibrils is preceded by the formation of toxic intermediates, which can interact with the cell membrane of surrounding cells and cause ionic influx, triggering the apoptosis cascade.
Formation of any amyloid fibril is a nucleationdependent process, and preformed fibrils may catalyse the conversion of a soluble protein to its fibrillar form. Human IAPP is a highly amyloidogenic peptide, and the release of insoluble intracellular aggregates into the extracellular space (e.g. by cell death) may stimulate the conversion of secreted IAPP. Consequently, elucidation of the initial step in amyloidogenesis, which may be an intracellular event, is particularly important.
Intracellular amyloid-like deposits contain unprocessed pro-islet amyloid polypeptide (proIAPP) in beta cells of transgenic mice overexpressing the gene for human IAPP and transplanted human islets.
J. F. Paulsson . A. Andersson . P. Westermark .G. T. Westermark
Diabetologia (2006) 49: 1237–1246
http://www.springerlink.com/content/w824704516157312/fulltext.pdf
Fig. 8 Proposed sequence of events leading to islet amyloidosis.
a First, the processing of proIAPP is affected by factors such as high levels of NEFAs or glucose. Granules with amyloid-like fibres fuse and form an intracellular proIAPP amyloid-like deposit.
b Over time this aggregate enlarges and replaces most of the cell.
c This cell dies and the amyloid becomes extracellular and can act as a template for further amyloid formation.
d Amyloid is now made up by IAPP secreted from neighbouring beta cells. Formation of extracellular amyloid fibrils is preceded by the formation of toxic intermediates, which can interact with the cell membrane of surrounding cells and cause ionic influx, triggering the apoptosis cascade.
Formation of any amyloid fibril is a nucleationdependent process, and preformed fibrils may catalyse the conversion of a soluble protein to its fibrillar form. Human IAPP is a highly amyloidogenic peptide, and the release of insoluble intracellular aggregates into the extracellular space (e.g. by cell death) may stimulate the conversion of secreted IAPP. Consequently, elucidation of the initial step in amyloidogenesis, which may be an intracellular event, is particularly important.
Friday, December 18, 2009
Thursday, December 17, 2009
Steered MD in GROMACS (pull code)
The pull code allows to apply a force between two centers of mass (for >1 groups). It appears to be useful to simulate protein penetration into lipid membrane (channel formation). Config must have a following lines:
pull_start = yes
pull_init1 = 0
pull = umbrella
pull_geometry = direction
pull_group0 = Protein
pull_group1 = POPC
pull_vec1 = 0 0 0.5
pull_k1 = 3000
pull_rate1 = 0.01 ; nm/ps Extreme parameters for extreme pulling
discussions: [1], [2]
pull_start = yes
pull_init1 = 0
pull = umbrella
pull_geometry = direction
pull_group0 = Protein
pull_group1 = POPC
pull_vec1 = 0 0 0.5
pull_k1 = 3000
pull_rate1 = 0.01 ; nm/ps Extreme parameters for extreme pulling
discussions: [1], [2]
Subscribe to:
Posts (Atom)