Biology – Quantitative Biology – Biomolecules
Scientific paper
2004-06-15
Biology
Quantitative Biology
Biomolecules
Scientific paper
10.1088/0953-8984/16/6/R02
While all the information required for the folding of a protein is contained in its amino acid sequence, one has not yet learned how to extract this information to predict the three--dimensional, biologically active, native conformation of a protein whose sequence is known. Using insight obtained from simple model simulations of the folding of proteins, in particular of the fact that this phenomenon is essentially controlled by conserved (native) contacts among (few) strongly interacting ("hot"), as a rule hydrophobic, amino acids, which also stabilize local elementary structures (LES, hidden, incipient secondary structures like $\alpha$--helices and $\beta$--sheets) formed early in the folding process and leading to the postcritical folding nucleus (i.e., the minimum set of native contacts which bring the system pass beyond the highest free--energy barrier found in the whole folding process) it is possible to work out a succesful strategy for reading the native structure of designed proteins from the knowledge of only their amino acid sequence and of the contact energies among the amino acids. Because LES have undergone millions of years of evolution to selectively dock to their complementary structures, small peptides made out of the same amino acids as the LES are expected to selectively attach to the newly expressed (unfolded) protein and inhibit its folding, or to the native (fluctuating) native conformation and denaturate it. These peptides, or their mimetic molecules, can thus be used as effective non--conventional drugs to those already existing (and directed at neutralizing the active site of enzymes), displaying the advantage of not suffering from the uprise of resistance.
Broglia Ricardo A.
Tiana Guido
No associations
LandOfFree
Simple models of protein folding and of non--conventional drug design does not yet have a rating. At this time, there are no reviews or comments for this scientific paper.
If you have personal experience with Simple models of protein folding and of non--conventional drug design, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Simple models of protein folding and of non--conventional drug design will most certainly appreciate the feedback.
Profile ID: LFWR-SCP-O-347436