The theme of this work is that of developing a useful, accurae science of forces that organize biomolecules. To this end we have concentrated our efforts to measure forces between proteins, DNA double helices, and polysaccharides. The Osmotic Stress method for direct force measurements is winning widespread use around the world. Our LSB home page contains """"""""living handbook"""""""" of osmotic stress data and calibration curves. Records indicate that the Page is accessed as often as once every couple of minutes. Current work on DNA forces combines osmotic stress with 31P-NMR, SAXS, and polarization microscopy. It has revealed a transition from high density hexatic phase with long-range hexagonal bond orientation and very limited DNA mobility to a liquid-like, low density cholesteric phase characterized by much greater motional freedom. Dialysis experiments at low osmotic pressures extended the range of previous force measurements demonstrating a new fluctuation-enhanced force regime. The strong analogy to flux lines in high temperature superconductors has brought a new kind of thinking to both subjects. This past year has seen the first quantitative measurement of the amount of water released upon the binding of various drugs to DNA. There is an immediate energetic connection between these changes in molecular hydration and the powerful """"""""hydration forces"""""""" measured between large molecules brought into contact. In our theoretical work, we have a way to explain the mysterious """"""""long-range hydrophobic force"""""""" through simple adsorption/desorption of the charged amphiphiles that create non-polar surfaces. This strategy provides a new way to analyze forces between surfaces to which small molecules can adsorb. A new set of studies on the coupling of intermolecular forces with molecular motion explains the long-range perturbation on motions of macromolecules in the presence of a wall such as a viral capsid or near an air/water interface. Computations of van der Waals forces between bilayers under different conditions have reconciled results from two different ways to measure bilayer-bilayer forces and now leads to a much more reliable use of measured bilayer interaction potentials.
