Aspectos especiais e temporais do problema do enovelamento protÃico

AUTOR(ES)
DATA DE PUBLICAÇÃO

2002

RESUMO

The manner in which a protein folds from a random coil into a unique native state in a relatively short time is one of the fundamental puzzles of molecular biophysics. It is well accepted that a unique native three-dimensional structure, characteristic of each protein and determined by the sequence of its amino-acids, dictates protein functions. In this Thesis two distinct approaches are considered to study general aspects of such problem: 1) a stochastic modeling of the backbone chain of the protein secondary structures to explore the general spacial aspects of the native state; 2) an analysis of the time evolution of the protein conformational potential energy calculated during the folding process mimicked by methods of molecular dynamics. In the first approach the proposed model generates a general backbone chain with a fixed fraction f of secondary like structures by means of a three-dimensional off-lattice random walk with fixed steps and the  and  dihedral angles within the peptide bonds chosen by Gaussian probability distributions. Such probability distributions have their mean value corresponding to the angles associated with the chosen secondary structures and the variance Â2 left as a free parameter to be determined. This model allows the construction of a great variety of backbone chains running from full random structures up to the biological ones observed in proteins. Some geometrical properties of globular structures, composed by a fraction f of Â-helix and/or b-strands, were particulary studied. The scaling behavior of the ratio of gyration (Rg) with the chain size (N); the degree of compactness (Â); the distribution of coordination number (zc) of the Carbon C atoms and energy involved on such contacts were explored and compared with data of hundreds of proteins extracted from the wwPDB (worldwide Protein Data Bank). The results indicate that simulated structures are more compact when a fraction of f ~ 0.6 of secondary portions (Â-helices and/or b-strands) are present than those built withbother sets of dihedral angles, whenever the standard deviation of the probability distributions are finite and close to  ~0:15. Independent of the details of all underlying physical chemistry mechanisms, building protein backbones with the method proposed in the present Thesis suggests that these structures are driven by narrow distributions leading to the conclusion that stochasticity has a fundamental role on the its compactness. The second approach investigate the multifractal properties of the time-series of the conformational energy of small Â-helix structures, in particular that of polyalanine family. Using the multifractal detrended fluctuation analysis method (MFDFA) the generalized Hurst exponent h(q) and its associated multifractal scaling exponent (q) were estimated for several time-series numerically generated by molecular dynamic simulations considering distinct initial configurations. Such simulations were done using the force field GROMOS implemented by the software THOR. In general, the analyzed time series exhibit a multifractal behavior, which depends on the number of residues N and the temperature T of the system. Furthermore, whenever represented by the h(q) or(q) spectra, the time-series multifractal properties reveal important aspects of the time evolution of the system. In particular, suggesting that the nucleation process of secondary structures, which should occurs during the walk of the protein on the corresponding portion of the conformational potential energy hyper-surface landscape, is essential for the folding process

ASSUNTO(S)

enovelamento protÃico sÃries temporais protein folding random-walks caminhantes aleatÃrios multifractals time series fisica multifractais

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