Johann Deisenhofer (2002) - Back to Proteins

Johann Deisenhofer (2002)

Back to Proteins

Johann Deisenhofer (2002)

Back to Proteins

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When Johann Deisenhofer attended the Lindau Nobel Laureate Meeting for the seventh time in 2002 („It is clear that I am a fan of the Lindau Meetings“, he opens his talk) he took the „overwhelming success“ of the genome project „contrary to some peoples’ expectations and skepticism“ as the starting point of his lecture. „Big Science has entered Biology“, he said. „We could see articles in top journals that had hundreds of authors, which reminded me of high-energy physics where this happened many years ago“. As a trained physicist who specialized in the determination of protein structures, Deisenhofer asks: „Can we repeat this big science approach with proteins?“If we pursued such a concerted approach that has become known under the name „structural genomics“, he says, we could undertake a massive parallel determination of protein structures instead of working at one protein at a time. Such an effort would not only make many structures in many folding stages available and ultimately allow for reliable structure predictions. It also provides new opportunities to target specific protein structures of pathogenic microorganisms and better combat infectious diseases that show rising incidence worldwide. „Many of us who have experienced the beginning of this field would have been really skeptical of the possibility of such a speed up ten years ago“, Deisenhofer expresses his optimism, before he shares with his audience four important words of caution:1. Many proteins probably will not cooperate because they are inaccessible for a fast automatic structural elucidation, e.g. membrane proteins. For the cytocrome bc1 complex it took eight years from “crystal to manuscript” for example. 2. The structure may not reveal the function of the protein. Synapsin proteins are abundant in our nerve cells and have been known for a long time, but nobody knows their function yet. 3. Evolution may have gone unexpected ways, so that conclusions from the bacterial to a mammalian version of a protein cannot easily or necessarily be drawn.4. Homology modeling is not yet precise enough to explain the chemistry of all proteins. This is especially true for enzymatic reactions, as the example of HMG CoA reductase shows. Besides that, Deisenhofer says, structural genomics produce data at a mind-boggling rate and require improved computational tools. “The ultimate goal is the simulation of whole cells and maybe even organisms. This is probably many decades away – but biology as a discipline can only be called successful when we have achieved this goal.”Joachim Pietzsch

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