C. Micheletti, F. Cecconi, A. Flammini and A. Maritan
Crucial stages of protein folding through a solvable model:
Predicting target sites for enzyme-inhibiting drugs
Protein Science, 11, 1878-1887 (2002).
Link to online article.
An exactly solvable model based on the topology of a protein native
state is applied to identify bottlenecks and key sites for the folding
of human immunodeficiency virus type 1 (HIV-1) protease. The predicted
sites are found to correlate well with clinical data on resistance to
Food and Drug Administration-approved drugs. It has been observed that
the effects of drug therapy are to induce multiple mutations on the
protease. The sites where such mutations occur correlate well with
those involved in folding bottlenecks identified through the
deterministic procedure proposed in this study. The high statistical
significance of the observed corre-lations suggests that the approach
may be promisingly used in conjunction with traditional techniques to
identify candidate locations for drug attacks.