00. Project Layout

Project Modules:

• • Multiple Sequence Alignment.

    • You can read more about it here.

    • You can get a set of tools from here

  • Structure Prediction.

    • You can read more about it here.

  • Homo-logy Modelling.

    • You can read more about it here.

    • You can get a set of tools from here.

Multiple Sequence Alignment:

• The original idea was to use Clustal W for MSA and generation of phylogenetic trees. Basically, as given in the introduction to the tool, Clustal W helps perform multiple sequence alignment for the unknown sequences given as a flat file format. In addition, it also creates Phylogenetic trees which can be used for evolutionary studies.

Homology modelling:

• • This is a part of Version 2.0 and beyond. Just a small intro of what lies ahead.

  • Create a complete visualization tool on the lines of SwissPDBViewer or PyMol.

• Basically the tool is supposed to consist of the following features:

  • • Visual interactive real time structure modifications.

    • Heat Map.

    • Ramachandran Plot.

    • Multiple Regression and Maximum Likelihood analysis.

    • H-Bond and S-Bond interactions.

    • Stereo studies.

    • Complete integration with the Structure Prediction Module.

      • Every time a new sequence model is created, there should be ability to auto export the model to this module rendered as a 3D structure.

      • The vice versa should also hold true. i.e., when we interact with the model and add or remove chains the subsequent changes should be easily aligned using msa and hmm.

• • Profile HMMs are built using a three step process.

    • hmmsearch - this step helps widen our horizon of search and provides suggestive leads from the set of databank.

    • hmmallign - this step helps perform the actual alignment.

    • hmmcalibrate - this step helps calibrate the aligned sequence for optimization of further searches.

• The big idea is to design my own algorithms, preferably in java

  • yeah! yeah! i know... slow, it is!

  • but then for web purposes java ee provides the most stable platform other than .net {i dont really know much about .net since in our days, .net was still very much a proprietary thingy, even for students!}; php is there but its just toooo scripty, doesn't have the solid feel of Objects; and then there's RoR but then that's too sketchy; so well, Java it is.

Structure Prediction:

• • This is the final step for Version 1.0

  • In the past, I have mostly relied on Modeller (written and compiled by Andrej Sali), but then I was a student and there were no Copyright issues.

  • Now, things have changed a lot. I am not a student anymore, and Andrej Sali has got kinda famous, so a little restrictive about the use of his software.

  • Nevertheless, the code is there upon request, and so far I remember, he once said he would only be too happy if the code could be ported to java by somebody else.

• Basically, modeller scripts work in the way as follows.

  • align: this module aligns the submitted sequences. Since our sequence is already aligned, it works faster. The algorithm used is different from the ones used above, so the accuracy is also improved.

• 1. Basically, it aligns a block of sequences with a block of structures. The gap penalty depends on the 3D structure of all sequences in block 1. The variable gap penalty can favor gaps in exposed regions, avoid gaps within secondary structure elements, favor gaps in curved parts of the main chain, and minimize the distance between the two positions spanning a gap. The modeller align command is preferred for aligning a sequence with structure(s) in comparative modeling because it tends to place gaps in a better structural context.

     • model: this module performs the actual modelling