User:Nathan H. Kipniss/Notebook/20.109 Final Project

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- Pharmaceutical companies often need to know how a drug is interacting with a target. These same techniques could be applied to calmodulin and its target, M13. I currently have a request with MIT libraries to purchase a critical paper (see below).
- Pharmaceutical companies often need to know how a drug is interacting with a target. These same techniques could be applied to calmodulin and its target, M13. I currently have a request with MIT libraries to purchase a critical paper (see below).
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==Papers and Summaries==
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Junker, JP et al. €œSingle-molecule force spectroscopy distinguishes target binding modes of calmodulin. Proceedings of the National Academy of Sciences of the United States of America 106.34 (2009): 14361-6.
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-Cooperativtiy in CaM and target proteins is target protein dependent.
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- Multiple transitions rates exist in CaM and target protein binding (again, protein dependent).
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- for skMLCK, one cooperative transition; no intermediates could be found with this approach.
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-potential issues: this paper uses worm like chain models to interpret data. How valid is that approximation/assumption?
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- this method slows kinetics to actually observe structural transitions
 +
-skMLCK demands that CaM is completely folded when binding.
 +
 +
==Papers Currently being read==
==Papers Currently being read==

Revision as of 12:43, 1 May 2012

Contents

Elucidating the function of D24H Inverse Pericam mutant

Background

In module 2 of 20.109, we created the D24H mutant of inverse pericam. The experimental results from the calcium binding assay was surprising as calcium affinity decreased (Kd increase), yet cooperativtiy increased. For a final research idea, I would like to propose the set of experiments that would elucidate how the addition of a histidine into the first binding loop of inverse pericam can make these changes.

[Media:S12_M2D7_TR-Orange.txt]

Fitted Matlab binding curves
Fitted Matlab binding curves

Ideas

-working under the assumption that the SDM did indeed work (sequencing with BLAST, discontinuous mega-blast suggests it did indeed work)

- consider looking at calmodulin only.

- Pharmaceutical companies often need to know how a drug is interacting with a target. These same techniques could be applied to calmodulin and its target, M13. I currently have a request with MIT libraries to purchase a critical paper (see below).


Papers and Summaries

Junker, JP et al. €œSingle-molecule force spectroscopy distinguishes target binding modes of calmodulin. Proceedings of the National Academy of Sciences of the United States of America 106.34 (2009): 14361-6.

-Cooperativtiy in CaM and target proteins is target protein dependent. - Multiple transitions rates exist in CaM and target protein binding (again, protein dependent). - for skMLCK, one cooperative transition; no intermediates could be found with this approach. -potential issues: this paper uses worm like chain models to interpret data. How valid is that approximation/assumption? - this method slows kinetics to actually observe structural transitions -skMLCK demands that CaM is completely folded when binding.


Papers Currently being read

Grossman,M et al. œAchieving broad molecular insights into dynamic protein interactions by integrated structural-kinetic approaches. Current opinion in structural biology 21.5 (2011): 678-85. Web. 1 Mar. 2012.

Scapin, G. Structural Biology and Drug Discovery. Current Pharmaceutical Design. 2006

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