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We present a method for designing a funnel-shaped free-energy surface that reproducibly assembles secondary structure elements of proteins into their native conformations from a random extended configuration. Assuming a priori knowledge of secondary structure, our method can design a funnel-shaped surface for folding of alpha, beta, and alphabeta structures individually. We design energy surfaces that fold up to five unrelated sequences with the same energy parameters. We develop a measure of the foldability of an energy landscape in silico and present an alternative way to view energy landscapes.

We introduce a method of looking at, analyzing, and comparing protein structures. The topology of a protein is captured by 30 numbers inspired by Vassiliev knot invariants. To illustrate the simplicity and power of this topological approach, we construct a measure (scaled Gauss metric, SGM) of similarity of protein shapes. Under this metric, protein chains naturally separate into fold clusters. We use SGM to construct an automatic classification procedure for the CATH2.4 database. The method is very fast because it requires neither alignment of the chains nor any chain-chain comparison. It also has only one adjustable parameter. We assign 95.51% of the chains into the proper C (class), A (architecture), T (topology), and H (homologous superfamily) fold, find all new folds, and detect no false geometric positives. Using the SGM, we display a "map" of the space of folds projected onto two dimensions, show the relative locations of the major structural classes, and "zoom into" the space of proteins to show architecture, topology, and fold clusters. The existence of a simple measure of a protein fold computed from the chain path will have a major impact on automatic fold classification.

We describe the construction of a scoring function designed to model the free energy of protein folding. An optimization technique is used to determine the best functional forms of the hydrophobic, residue-residue and hydrogen-bonding components of the potential. The scoring function is expanded by use of Chebyshev polynomials, the coefficients of which are determined by minimizing the score, in units of standard deviation, of native structures in the ensembles of alternate decoy conformations. The derived effective potential is then tested on decoy sets used conventionally in such studies. Using our scoring function, we achieve a high level of discrimination between correct and incorrect folds. In addition, our method is able to represent functions of arbitrary shape with fewer parameters than the usual histogram potentials of similar resolution. Finally, our representation can be combined easily with many optimization methods, because the total energy is a linear function of the parameters. Our results show that the techniques of Z-score optimization and Chebyshev expansion work well.

We present a novel technique of sampling the configurations of helical proteins. Assuming knowledge of native secondary structure, we employ assembly rules gathered from a database of existing structures to enumerate the geometrically possible three-dimensional arrangements of the constituent helices. We produce a library of possible folds for 25 helical protein cores. In each case, our method finds significant numbers of conformations close to the native structure. In addition, we assign coordinates to all atoms for four of the 25 proteins and show that this has a small effect on the number of near-native conformations. In the context of database driven exhaustive enumeration our method performs extremely well, yielding significant percentages of conformations (between 0.02% and 82%) within 6 A of the native structure. The method's speed and efficiency make it a valuable tool for predicting protein structure., (Copyright 2001 Academic Press.)

We examine the conformations of a model for a short segment of closed DNA. The molecule is represented as a cylindrically symmetric elastic rod with a constraint corresponding to a specification of the linking number. We obtain analytic expressions leading to the spatial configuration of a family of solutions representing distortions that interpolate between the circular form of DNA and a figure-eight form that represents the onset of interwinding. We are also able to generate knotted loops. We suggest ways to use our approach to produce other configurations relevant to studies of DNA structure. The stability of the distorted configurations is assessed, along with the effects of fluctuations on the free energy of the various configurations.

One peculiarity of pulmonary surfactant, which is the tensioactive material physiologically present at the surface of alveoli, lies in its very quick localization at in the air-water interface. This being one of the limiting factors of artificial exogenous surfactants for the treatment of patients suffering of respiratory distress syndromes, we have studied the mechanisms which are intervening in the adsorption kinetics of a pure liquid--phase phospholipid, the dioleylphosphatidylcholine (DOPC), and of mixtures of dipalmitoylphosphatidylcholine (DPPC) and phosphatidic acid (PA) in presence of divalent cations (Ca++ and Mg++). The adsorption kinetics of liposomal suspensions of DOPC, which were studied by the Wilhelmy plate method, are determined by the existence of a barrier potential which height depends on the temperature and medium osmolarity, and on the deformability of vesicules. The study of PA-DPPC liposomes was performed with the help of a pulsating bubble surfactometer, a physicochemical instrumentation which mimics the pulmonary alveoli. To obtain performant responses with this model, high concentrations of PA and of divalent cations Ca++ and Mg++ are needed. These results, which are similar to those observed during the study of liposomal fusion, allow to propose a model, according to which adsorption of liposomes at the air-water interface is comparable to liposomal fusion and may be related to the presence of a thin aqueous film.

Eye metastases in carcinoma of the cervix are very rare, although not an uncommon presentation of carcinomas in general. A patient with eye symptoms secondary to retro-ocular metastatic carcinoma of the cervix is presented.

A patient with adult onset of the tethered cord syndrome is described. The significance of the clinical presentation and the myelographic and computed tomographic findings are discussed.

A case of a large exophytic renal angiomyolipoma is presented. Despite the features on excretory urography suggestive of an extrarenal mass, computed tomography provided information concerning the origin and pathological nature of the lesion.