Week+of+11-15-09

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I've decided that since all this is going to be better organized on the main page anyway, I can use separate pages and it'll be fine.

=NPC2= A smaller, soluble glycoprotein, it facilitates primarily cholesterol (but also other lipids) egress from the endosomal/lysosomal compartment, and plays a role in regulating homeostasis. It has five regions of interest, including a hydrophobic "knob" most likely involved in membrane interaction, the cholesterol binding region itself, and three faces that are likely involved in mediating separate interactions.

How to analyze - and why
Several attempts have been made to determine exactly how NPC1 and NPC2 carry out the transport of cholesterol in a cell. As of yet, none of them have yielded much success. One such approach is to identify mutations in the genetic coding for NPC2 and correlate them with the disease. However, there is only a small number of missense mutations that have been identified. Another approach is to look at the primary sequence of amino acids and see which regions are evolutionarily conserved (that is, are relatively constant in many species). This can identify which regions are most likely involved in interactions, as the more functionally significant regions are likely to remain more stable between species than those simply exposed to the cytosol. However, analysis of the primary sequence alone is likely insufficient, as amino acids can have similar primary sequences but very different tertiary structures, and vice versa.

To this end, Dr. HG and her colleagues focused on modeling the surface conservation and composition, forming images and studies in three dimensions. By doing so, they identified the same four regions as Dr. Ko and his colleagues, but also improved upon the clarity and resolution of these regions. In addition, another region was identified, the aforementioned hydrophobic "knob" on the exterior of the protein. It is poorly conserved in primary structure, but is very well conserved in tertiary structure and being hydrophobic overall.

The procedure to obtain such a well-defined result via observation of molecular evolution is as follows:
 * Select a group of sufficiently diverse animals
 * Align the sequences for the desired protein(s)
 * Calculate conservation scores (number of "hits" for similar sequence segments)[[image:2009-11-30_1959.png link="@http://docs.google.com/gview?a=v&pid=gmail&attid=0.1&thid=1247752f18618830&mt=application/pdf&url=http://mail.google.com/mail/%3Fui%3D2%26ik%3D67e2a28b11%26view%3Datt%26th%3D1247752f18618830%26attid%3D0.1%26disp%3Dattd%26zw&sig=AHIEtbR54GGT4cCM3eP2FhqbQYog-9xn7A"]]
 * Convert ranges of the scores to colors and map the score onto a three dimensional structure of the protein

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