PHYSICAL PRINCIPLES OF BIOMOLECULAR RECOGNITION, SELF ASSEMBLY & REGULATION

许多必需的大分子复合物的形成和功能 生物体依赖于它们的螺旋之间的相互作用 成分：α-螺旋，DNA，胶原蛋白等。我们开发了一个理论， 与以前的模型不同，这种螺旋之间的力占 对于带电和溶剂化残基的实际离散模式， 分子表面这一理论揭示了 分子结构和分子间力。它解释说， 现象为：DNA“过度缠绕”，从溶液中的10.5 bp/圈到10 纤维中的bp/转角; DNA凝聚中的互补特异性;以及 在过去15 A的分离过程中观察到的不寻常的力特征 DNA胶原蛋白和四链鸟苷螺旋之间的联系我们 继续进行实验研究， I型胶原蛋白的三股螺旋。这是最丰富的螺旋 人体内的蛋白质。它是骨骼中的主要结构蛋白， 肌腱皮肤和其他组织我们之前观察到一个短距离的 （0至8 A），指数排斥，阻止了分子接触 胶原蛋白螺旋之间，以及更长范围的，温度依赖性 使螺旋自发组装成纤维的吸引力 超过30摄氏度。在过去的一年里，我们证明， 排斥是由于氢键网络的能量消耗 在中间水层中的重排。吸引力 显然与形成更具体的氢键有关 水分子团簇桥接了对面的未知识别位点， 螺旋我们发现糖和多元醇降低了 通过破坏胶原纤维和干扰胶原纤维形成 这些水团。人们可以推测， 开链葡萄糖共价连接在识别位点处或附近 可能是胶原纤维和结缔组织损伤的主要原因 糖尿病的失败是一种严重的，有时是致命的 死亡的并发症。这一假设需要进一步检验。

Formation and function of many essential macromolecular complexes in living organisms depends on interactions between their helical components: alpha-helices, DNA, collagen, etc. We developed a theory of forces between such helices which, unlike previous models, accounted for realistic, discrete patterns of charged and solvated residues on the molecular surfaces. This theory revealed a relationship between the molecular structure and intermolecular forces. It explained such phenomena as: DNA "overwinding" from 10.5 bp/turn in solution to 10 bp/turn in fibers; counterion specificity in DNA condensation; and unusual force features observed over the last 15 A of separation between DNA, collagen, and four-stranded guanosine helices. We continued experimental study of the nature of interactions between triple helices of type I collagen. This is the most abundant helical protein in the human body. It is a major structural protein in bones, tendons, skin, and other tissues. We previously observed a short-range (0 to 8 A), exponential repulsion, which prevented the molecular contact between collagen helices, and a longer-range, temperature-dependent attraction which caused spontaneous assembly of the helices into fibers above 30 degrees C. During the past year we demonstrated that the repulsion is due to the energetic cost of a hydrogen-bond network rearrangement in the intervening water layer. The attraction is apparently associated with formation of more specific hydrogen-bonded water clusters bridging still unknown recognition sites on the opposing helices. We discovered that sugars and polyols reduce the stability of collagen fibers and interfere with collagen fibrillogenesis by disrupting these water clusters. One may speculate that slow accumulation of an open-chain glucose covalently attached at or near the recognition sites may be the main cause of collagen fiber damage and connective tissue failure in diabetes which is as a serious and sometimes fatal complication of the decease. This hypothesis requires further testing.