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| Andrew Pohorill, NASA Ames Research Center |
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| Andrew Pohorille received Ph.D. in biophysics from the Department of Physics, University of Warsaw in 1979. He obtained his postdoctoral training with Prof. Bernard Pullman at the Institute de Biologie Chimico-Physique in Paris. Between 1982 and 1992 he was on the research faculty at the Department of Chemistry, University of California, Berkeley. Since 1992 he has been professor of Chemistry and Pharmaceutical Chemistry at the University of California San Francisco. In 1996 he joined the staff of the Exobiology Branch at NASA-Ames. Currently he heads the NASA Center for Computational Astrobiology and Fundamental Biology. In 2000 he received the NASA Group Award as a member of the Astrobiology Team and in 2002 he was awarded the NASA Exceptional Scientific Achievement Medal. His main interests have been centered on simulating the structure and function of biomolecular and cellular systems, and in particular membranes and membrane proteins. He also has a long-standing interest in the nature of hydrophobic effects and aqueous solution interfaces. His other research activities are devoted to computational modeling of genetic and regulatory networks, the mechanism of anesthetic action, the origin of life, the structure of comets and mathematical models of making risky decision. He also works on the development of new computational methods and algorithms particularly suitable for parallel and distributed computing. He co-authored over 80 peer-reviewed publications in these and related areas.
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Structure, Function, Self-assembly and Origin of Simple Membrane Proteins
Andrew Pohorill, NASA Ames Research Center
Integral membrane proteins perform such essential cellular functions as transport of ions, nutrients and waste products across cell walls, transduction of environmental signals, regulation of cell fusion, recognition of other cells, energy capture and its conversion into high-energy compounds. In fact, 30% of genes in modern organisms codes for membrane proteins.
Although contemporary membrane proteins or their functional assemblies are quite complex, their transmembrane fragments are remarkably simple. Their most common structural motif is a bundle of alpha-helices. In a series of molecular dynamics computer simulations we investigated self-organizing properties of simple membrane proteins based on this structural motif. Specifically, we studied folding and insertion into membranes of short, nonpolar or amphiphatic peptides. We also investigated glycophorin A, a peptide that forms sequence-specific dimers, and a transmembrane aggregate of four identical alpha-helices that forms an efficient and selective voltage-gated proton channel.
Many peptides are attracted to water-membrane interfaces. Once at the interface, nonpolar peptides spontaneously fold to alpha-helices. Whenever the sequence permits, peptides that contain both polar and nonpolar amino also adopt helical structures, in which polar and nonpolar amino acids are immersed in water and membrane, respectively. Specific identity of side chains is less important. Helical peptides at the interface could insert into the membrane and adopt a transmembrane orientation. This is, however, unfavorable because polar groups in the peptide become completely dehydrated.
The unfavorable free energy of insertion can be regained through association of helices in the membrane. These helical bundles could form channels capable of transporting ions and small molecules across membranes. Stability of transmembrane aggregates of simple proteins is often only marginal and, therefore, it can be regulated by environmental signals or small sequence modifications.
A key step in the earliest evolution of membrane proteins was the emergence of selectivity for specific substrates. Many channels could become selective if one or only a few properly chosen amino acids are properly placed along the channel, acting as filters or gates. This is a convenient evolutionary solution because it does not require imposing conditions on the whole sequence.
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