On the prediction and design of globular proteins structure

RENZI, DANILO G.; STOICO, CÉSAR O.; VERICAT, FERNANDO

Montevideo, Uruguay

Congreso; 6th International Conference of Biological Physics (ICBP); 2007

International Union of Pure and Applied Biophysics (IUPAB)

One of the challenges of the modern molecular biology is the prediction of the proteins native structure from the knowledge of their amino acid sequence under normal physiological conditions. To have at one's disposal such a code should help us, for example, to modify in a predictable way the function of several natural proteins by introducing appropriate mutations.  Also, it should make easier the design of new amino acids sequences in order to fulfil specific functions. In some sense prediction and design can be thought as to aspects of the same phenomenon. In the first case one intend to find the native structure corresponding to a given sequence; in the second one the problem is to determine the amino acids sequence which gives a structure given a priori. In this communication, we attempt to obtain some information about this two aspects by studying the relation between energy, sequence and spatial configuration. Using for the interactions  between pairs of amino acids those potentials of mean force we obtain from a theory of classical liquids, we calculate: i) for a given amino acids sequence the energy of the corresponding native structure and of another structures which are obtained by perturbing the original one; ii) for a given native structure, the energy for the corresponding sequence and also for other sequences derived from the original one by introducing several mutations. In all the cases we use for the native structure the one obtained from x-ray diffraction experiments on crystallized proteins as taken from the Protein Data Bank