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.
