PDF《arXiv:0705.1845v1 [physics.bio-ph]》

? control the passage of species through the membranes of cells and or- ganelles;

? control gene expression;

? are the essential agents in the transcription of the genetic information into more proteins;

? together with some nucleic acids, form the ribosome, the large molecular organelle where proteins themselves are synthesized;

? as chaperones, protect other proteins to help them to acquire their func- tional three-dimensional structure. Due to this participation in almost every task that is essential for life, protein science constitutes a support of increasing importance for the development of modern Medicine. On one side, the lack or malfunction of particular proteins is behind many pathologies;

e.g., in most types of cancer, mutations are found in

2 Figure 1.1: Four molecular machines formed principally by proteins. Figures taken from the Molecule of the month section of the RSCB Protein Data Bank (http://www.pdb.org), we thank the RSCB PDB and David S. Goodsell, from the Scripps Research Institute, for kind permission to use them. (a) ATP synthase: it acts as an energy generator when it is traversed by protons that make its two cou- pled engines rotate in reverse mode and the ATP molecule is produced. (b) RNA polymerase: it slides along a thread of DNA reading the base pairs and synthesizing a matching copy of RNA. (c) GroEL-GroES complex: it helps unfolded proteins to fold by sheltering them from the overcrowded cellular cytoplasm. (d) Ribosome: it polymerizes amino acids to form proteins following the instructions written in a thread of mRNA.

3 the tumor suppressor p53 protein [2]. Also, abnormal protein aggregation char- acterizes many neurodegenerative disorders, including Huntington, Alzheimer, Creutzfeld-Jakob ('

mad cow'

), or motor neuron diseases [3C5]. Finally, to at- tack the vital proteins of pathogens (HIV [6, 7], SARS [8], hepatitis [9], etc.), or to block the synthesis of proteins at the bacterial ribosome [10], are common strategies to battle infections in the frenetic ?eld of rational drug design [11]. Apart from Medicine, the rest of human technology may also bene?t from the solutions that Nature, after thousands of millions1 of years of '

research'

, has found to the typical practical problems. And that solutions are often proteins: New materials of extraordinary mechanical properties could be designed from the basis of the spider silk [12, 13], elastin [14] or collagen proteins [15]. Also, some attempts are being made to integrate these new biomaterials with living organic tissues and make them respond to stimuli [16]. Even further away on the road that goes from passive structural functions to active tasks, no engineer who has ever tried to solve a di?cult chemical problem can avoid to experience a feeling of almost religious inferiority when faced to the speed, e?ciency and speci?city with which proteins cut, bend, repair, carry, link or modify other chemical species. Hence, it is normal that we play with the idea of learning to control that power and have, as a result, nanoengines, nanogenerators, nanoscis- sors, nanomachines in general [17]. The author of this work, in particular, felt a small sting of awe when he learnt about the pump and the two coupled engines of the principal energy generator in the cell, the ATP synthase (?gure 1.1a);

about the genetic Xerox machine, the RNA polymerase (?gure 1.1b);

about the hut where the proteins fold under shelter, the GroEL-GroES complex (?gure 1.1c);

or about the macromolecular factory where proteins are created, the ribosome (?gure 1.1d), to mention four specially impressive examples. Agreeing again with Lesk [1]: Proteins are fascinating molecular devices. From a more academic standpoint, proteins are proving to be a powerful centre of interdisciplinary research, making many diverse ?elds and people with di?erent formations come in contact2 . Proteins force biologists, biochemists and chemists to learn more physics, mathematics and computation and force mathematicians, physicists and computer technicians to learn more biology, bio- chemistry and chemistry. This, indeed, cannot be negative. In 2005, in a special section of Science magazine entitled '