The ion channel forming peptide gramicidin A adopts a number of distinct conformations in different environments. We have developed a new method to analyze and display the pore dimensions of ion channels. The procedure is applied to two x-ray crystal structures of gramicidin that adopt distinct antiparallel double helical dimer conformations and a nuclear magnetic resonance (NMR) structure for the beta6.3 NH2-terminal to NH2-terminal dimer. The results are discussed with reference to ion conductance properties and dependence of pore dimensions on the environment.

We have analyzed the buried water molecules and internal cavities in a set of 75 high-resolution, nonhomologous, monomeric protein structures. The number of hydrogen bonds formed between each water molecule and the protein varies from 0 to 4, with 3 being most common. Nearly half of the water molecules are found in pairs or larger clusters. Approximately 90% are shown to be associated with large cavities within the protein, as determined by a novel program, PRO-ACT. The total volume of a protein's large cavities is proportional to its molecular weight and is not dependent on structural class. The largest cavities in proteins are generally elongated rather than globular. There are many more empty cavities than hydrated cavities. The likelihood of a cavity being occupied by a water molecule increases with cavity size and the number of available hydrogen bond partners, with each additional partner typically stabilizing the occupied state by 0.6 kcal/mol.

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A novel modelling procedure, which rapidly unfolds a protein by enhancing solvent penetration of its core, was used to investigate the unfolding pathway of hen egg-white lysozyme. Early on the unfolding pathway there is a dramatic disruption of the tertiary contacts within the protein, which decouples its domains. Subsequently, the helical domain slowly loses its compactness and the helices fluctuate rapidly. The protein then adopts a 'molten globule-like' structure in which the native beta-sheet is essentially intact. The modelled structures have properties similar to those of lysozyme's experimentally characterized partially folded states and provide insight into its complex (un)folding process. The sequence of unfolding events shows how the unfolding pathway of a multidomain protein may be most similar to its fastest, but not necessarily its dominant, folding pathway.

SUMMARY1. The swelling characteristics of demembranated bovine corneal stroma were studied as a function of time and of the pH and ionic strength of the bathing solution.2. Compared with other pH values, the stroma swelled least near pH 4. 3. In the pH range 6-10, increasing the pH resulted in an increase both in the rate of swelling and in the hydration reached in a given time.4. At pH 2 and 4, a final constant value of hydration was attained. At higher pH values no such equilibrium was attained when the hydration of the tissue was followed for at least 100 hr.5. The swelling at high pH values was consistent with the hypothesis that the Donnan-osmotic contribution is the major component of the swelling pressure.6. The ionic strength dependence was complex. There was a general decrease of swelling with increase in the ionic strength (iu) until around /t = 0-1. The swelling at u=0-15 was greater than at /= 0-1 and 1z = 0-25. 7. The results were interpreted on the assumption that the Donnan-osmotic effect is the major component of the swelling pressure.