From Jishu Csgrad
Date: Tue, 23 Mar 2004 18:54:33 -0500 (EST)
From: Jiang Shu <>
To:
Cc: <>, <>, <>
Subject: Pathfinder Progress Report
Hi Dr. Onufriev,
This is Pathfinder's progress report. Sorry for sending it late.
Basically, we are still trying to validate the result of our cavity search program, by theory and by visualizing it. We tried some snapshots that you gave us, but we haven't processed all the snapshots. Below are the progress reports from each of us.
Jiang Shu
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What works:
1) I worked on a little program to convert Deept's output (logger.txt) to a file in PDB format.
2) I plotted Deept's cavity search program results by using MSMS+Raster3D.
Please refer to the link "e5" on our project web page.
3) I kept updating our web page showing our progress...
4) I kept emailing my team members for progress...
What does not work:
1) Once I am using the actual radius of the oxygen, the Raster3D render complain the size the objects and the size of the short array to handle the shadow detail.
2) The Raster3D's render on Chekhov can't handle the number of graphical objects we are dealing with (no matter it is "the published cavites" or "our cavity findings"). My Sun workstation can handle 10 times of Chekhov, but still not enough.
What I will work on:
1) Play with "ulimit" see if I can make render to plot more objects.
2) I want to compare Deept's output with the published cavities by making a little animation - using djpeg and whirlgif...
Deept Kumar
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What I have been working on:
1) Worked on the code for the cavity finding to check for connected components with at least k empty cells.
2) Worked on modifying the code for finding volume for the structure.
Yet to finish:
1) Finalize the above 2 items.
2) A sample run using about 100 frames will be done.
Maulik Shukla
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What works:
1) I looked at some references regarding known cavities in myoglobin.
2) I managed our class website. It is now working at new address:
I will add on stuff as I receive from the groups.
What I will work on:
1) Compare myoglobin volume calculated by Deept's program with that obtained using other sofwares like MSMS and Voidoo. I will work on it once I get results from Deept.
Nilanjan Saha
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What I have been working on:
I have been reading some papers on oxygen affinity of Myoglobin and Hemoglobin. I found something very interesting. When oxygen binds to the first subunit of deoxyhemoglobin it increases the affinity of the remaining subunits for oxygen. I have also gathered some information about Myoglobin that we might need while writing the paper.
1)
The tertiary structure of myoglobin is that of a typical water soluble globular protein. Its secondary structure is unusual in that it contains a very high proportion (75%) of a-helical secondary structure. A myoglobin polypeptide is comprised of 8 separate right handed a-helices, designated A through H, that are connected by short non helical regions. Amino acid R-groups packed into the interior of the molecule are predominantly hydrophobic in character while those exposed on the surface of the molecule are generally hydrophilic, thus making the molecule relatively water soluble. Each myoglobin molecule contains one heme prosthetic group inserted into a hydrophobic cleft in the protein. Each heme residue contains one central coordinately bound iron atom that is normally in the Fe2+, or ferrous, oxidation state. The oxygen carried by hemeproteins is bound directly to the ferrous iron atom of the heme prosthetic group.
Oxidation of the iron to the Fe3+, ferric, oxidation state renders the molecule incapable of normal oxygen binding. Hydrophobic interactions between the tetrapyrrole ring and hydrophobic amino acid R groups on the interior of the cleft in the protein strongly stabilize the heme protein conjugate. In addition a nitrogen atom from a histidine R group located above the plane of the heme ring is coordinated with the iron atom further stabilizing the interaction between the heme and the protein. In oxymyoglobin, the remaining bonding site on the iron atom (the 6th coordinate position) is occupied by the oxygen, whose binding is stabilized by a second histidine residue.
2)
Computer simulations of the behavior of oxymyoglobin suggest that the rate-limiting process in oxygen release is the opening of a pathway for the O2 molecule to escape from the heme pocket. Oxygen may spend time "rattling in its cage" - and perhaps being recaptured - before the tertiary structure of the myoglobin shifts enough to let it escape (Figure 7.7). This process is an explicit example of a principle set forth elsewhere (here) - the dynamic internal motions of globular protein molecules play important roles in regulating the processes proteins mediate. The flexibility of myoglobin may thus determine how strongly myoglobin binds oxygen.