teractions between various biological helices control protein folding and assembly, DNA packing, protein-DNA interactions, connective tissue formation and stability, and many other processes responsible for normal function and pathology in living organisms. By combining direct measurements with rigorous physical theories we continued to advance our understanding of these most basic molecular recognition reactions. Our most significant achievements during the past year were: (1) Development of a theory of electrostatic interactions driving poly- and mesomorphous transitions in dense aggregates of long, natural DNA. Based on this theory, we proposed mechanisms for the B to A transition in DNA fibers upon decreasing humidity, for the stabilization of the B form by Li+ ions, and for the transitions from hexagonal to monoclinic or orthorhombic packing of DNA in the aggregates. These phenomena were observed already in early, pioneering studies by Franklin et al. and by Wilkins et al., but they were never fully understood. (2) Measurement of the effects of protein denaturants on interactions between collagen helices in fibers. Our results suggested a novel mechanism of temperature-induced collagen fibrillogenesis. Apparently, elevated temperature causes local melting and structural rearrangements of collagen triple helices in a vicinity of recognition sites. This promotes correct inter-molecular recognition and fiber assembly. Urea, acetamide, and some of their methylated derivatives facilitate the process by easing the local melting. As a result, they enhance the temperature dependence of forces between collagen helices. However, these protein denaturants also bind non-specifically to collagen backbone intensifying hydration repulsion between triple helices. The latter effect, which is likely to be common for most proteins, overpowers the recognition enhancement leading to overall suppression of fibrillogenesis.""""""""

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Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Intramural Research (Z01)
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Special Emphasis Panel (LPSB)
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