The entropy production rate was determined for avascular tumor growth. The proposed formula relates the fractal dimension of the tumor contour with the quotient between mitosis and apoptosis rate, which can be used to characterize the degree of proliferation of tumor cells. The entropy production rate was determined for fourteen tumor cell lines as a physical function of cancer robustness. The entropy production rate is a hallmark that allows us the possibility of prognosis of tumor proliferation and invasion capacities, key fac-tors to improve cancer therapy

Predictive Quantitative Structure-Activity Relationship (QSAR) models of anabolic and androgenic activities for the 17b-hydroxy-5a-androstane steroid family were obtained by means of multi-linear regression using quantum and physicochemical molecular descriptors and a genetic algorithm for the selection of the best set of descriptors. The model allows the identification, selection and future design of new steroid molecules with increased anabolic activity. Molecular descriptors included in reported models allow the structural interpretation of the biological process, evidencing the main role of the shape of molecules, hydrophobicity and electronic properties. The model for the anabolic/ androgenic ratio (expressed by the weight of the levator ani muscle and ventral prostate in mice) predicts that: a) 2-cyano-17-a-methyl-17-b-acetoxy-5a-androst-2-ene is the most potent anabolic steroid in the group and b) the testosterone-3-cyclopentenyl-enoleter is the less potent one. The approach described in this paper is an alternative for the discovery and optimization of leading anabolic compounds.

The IA(3) polypeptide inhibitor from Saccharomyces cerevisiae interacts potently and selectively with its target, the S. cerevisiae vacuolar aspartic proteinase (ScPr). Upon encountering the enzyme, residues 2-32 of the intrinsically unstructured IA(3) polypeptide become ordered into an almost-perfect alpha-helix. In previous IA(3) mutagenesis studies, we identified important characteristics of the enzyme inhibitor interactions and generated a large dataset of variants with K(i) values determined experimentally at pH 3.1 and 4.7. Using this information, the three-dimensional structure of each variant was modelled in silico with the correct protonation for each experimental pH value. A set of descriptors of the inhibitor/ScPr interactions was then calculated and used to establish mathematical models relating the variant sequences to their inhibitory activities at each pH. Cross-validation, external-set validation and five separate selections of the training and test samples confirmed the robustness of the equations. A major contributor to the structure-activity relationship was the free energy of binding calculated by the FoldX program. The mathematical models were challenged further (i) by in silico alanine-scanning mutagenesis of residues 2-32 in IA(3) and relating binding energy to experimentally derived inhibition constants for selected representatives of these variants; and (ii) by predicting inhibitory-potencies for two novel IA(3)-variants. The predictions of the equations for these new IA(3)-variants with ScPr matched almost precisely the kinetic data determined experimentally. The models described represent valuable tools for the future design of novel inhibitor variants active against ScPr and other aspartic proteinases.

The determination of the stereochemistry of brasinosteroid analogs with 22,23-epoxide groups can be easily achieved by means of (13)C NMR spectroscopy. Here, we provide a rationalization of the (13)C chemical shift pattern found in 22R,23R- and 22S,23S-epoxides of stigmasterol, based on the analysis of gamma effects. (22S,23S)- and (22R,23R)-3beta-acetoxystigmast-22,23-epoxy-5,6beta-diol were used in the study as model compounds. Our methodology starts with a conformational search by means of molecular dynamics and NMR (NOE contacts) spectroscopy, which is followed by the analysis of the different gamma interactions affecting the chemical shift of interest. We demonstrate that the differences between the (13)C chemical shift patterns of 22R,23R and 22S,23S isomers arise from gamma effects as the result of diverging local conformations around the C17-C20 and C20-C22 bonds.