Physical Principles of Biomolecular Recognition, Self-Assembly and Regulation

各种生物螺旋之间的相互作用 控制蛋白质折叠和组装，DNA包装，蛋白质-DNA 相互作用，结缔组织形成和稳定，以及许多 其他负责正常功能和病理的过程 活的有机体通过将直接测量与严格的 我们继续推进我们对物理理论的理解 这些最基本的分子识别反应我们最 过去一年的主要工作包括：（一） 静电相互作用驱动多聚体的理论发展 和长， 天然DNA基于这一理论，我们提出了 DNA纤维中的B到A的转变 湿度，用于通过Li+离子稳定B形式，以及用于 从六方到单斜或正交的过渡 聚集体中DNA的包装。这些现象 富兰克林等人在早期的开创性研究中已经观察到， 由Wilkins等人，但他们从未被完全理解。（二） 蛋白质变性剂对相互作用的影响的测量 胶原蛋白螺旋之间的联系我们的研究结果表明， 温度诱导胶原原纤维形成的机制。 显然，温度升高会导致局部融化， 胶原蛋白三螺旋结构重排在附近的 识别位点。这促进了正确的分子间识别 和纤维组装。尿素，乙酰胺，以及它们的一些 甲基化的衍生物通过缓解局部 融化结果，它们增强了温度依赖性 胶原蛋白螺旋之间的作用力。然而，这些蛋白质 变性剂也非特异性地结合胶原骨架 增强了三股螺旋之间的水化排斥作用。后者 效应，这可能是常见的大多数蛋白质， 超过识别增强，导致整体 抑制纤维形成。"

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."