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Volume IV Issue 8 - April 19,
2000
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UNIVERSITY OF CALIFORNIA, SAN DIEGO — Sometimes, bacteria can be great. SDSC chemist and principal scientist Kim Baldridge is studying bacteriochlorophyll, a substance that can be extracted from certain kinds of bacteria, in a collaboration with graduate student Roie Yerushalmi, a member of Professor Avigdor Scherz's group of the Weizmann Institute of Science in Israel. The goal is to combine the computational aspect of SDSC with the experimental aspect of the group in Israel, to find out more about this molecule and how it reacts. One of the potential benefits of such research is to help in the design of new derivatives of bacteriochlorophyll as key components in photodynamic therapy for the treatment of cancer.
"The power of this research is in linking the computational with the experimental," Baldridge said. "This combination has allowed us to elucidate more information on this topic than either group by itself. And we've been able to make key statements because of the unique collaborative approaches we have taken."
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Two views of a nickel-bacteriochlorophyll structure with an imidazole ligand. Imidazole, used chiefly in organic synthesis, is shown bonded to the central metal atom, which is nickel in this case. |
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Recent developments in the search for better treatment of cancer have led to wider acceptance of photodynamic therapy, the localized treatment of tumors via illumination of light-sensitive molecules that are introduced into the human body. In the search for appropriate light-sensitive molecules, or photosensitizers, bacteriochlorophyll appears to have some advantages over Photofrin, the most common photosensitizer for such therapy. Bacteriochlorophyll, when illuminated, can cause the light to reach deeper into tissue, thereby being more effective for larger tumors.
Bacteriochlorophyll is a form of chlorophyll in some bacteria that performs photosynthesis, the use of light as a source of energy to propel the conversion of carbon dioxide, water, and inorganic salts into complex organic materials like carbohydrates, for sustenance. Unlike chlorophyll, the green matter found in plants, bacteriochlorophyll does not need oxygen for photosynthesis.
Bacteriochlorophyll can be modified, both its electronic properties, as well as for basic science, thereby demonstrating both the fundamental principles of chemistry as well as the molecules use in photodynamic therapy. These modifications include substituting the central metal atom, magnesium, with other metal atoms such as nickel. Another modification is to bond a ligand (an atom or molecule that bonds in an axial manner to the central metal atom) using the bacteriochlorophyll frame to study ligands of biological interest.
"Using SDSC's computational abilities, we are better able to understand these systems," Yerushalmi said. "Besides the theoretical studies, there are also implications for basic science, and we can implement the knowledge we gain here to the other side of the group doing the experimental studies. With a better understanding of the basic phenomena in the chemistry of such systems, this research can be very important, for example, in the development of anti-cancer drugs."
For this research, Baldridge's group has been using Blue Horizon at SDSC, as well as a cluster of COMPAQ workstations which have been recently acquired by the group.
"We can do detailed computational modeling, which is viable to the study of larger compounds using the experimental theories from the Israel group," Baldridge said. "The results of the computation can help corroborate the empirical relationships that are being set out from the experimental studies."
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The group used the GAMESS (General Atomic and Molecular Electronic Structure System) software, of which Baldridge is one of the authors. Much effort has gone into the parallelization of the code use d for the computations on many of the available platforms these days. GAMESS is an ab initio molecular program. In addition, QMView was invoked for analysis and visualization of the computed results (see inset photos). This software, developed by Baldridge and Jerry Greenberg, a computational chemist at SDSC, has been customized to sort out all the data for this project. QMView is a graphical chemistry program that runs on UNIX TM workstations that support OpenGLTM. New features were added to the code for the visualization of the surfaces shown the second set of the inset figures.
"This is an ongoing effort. The greatest impact is on photodynamic modeling," Baldridge said. "I think it is powerful research, and additionally, incredibly interesting. In developing new procedures, not only have we been able to have new analysis tools from the theories available to us, but we can influence cancer research in the long-term." —AV