Two deterministic models for Brownian motion are investigated by means of numerical simulations and kinetic theory arguments. The first model consists of a heavy hard disk immersed in a rarefied gas of smaller and lighter hard disks acting as a therm
al bath. The second is the same except for the shape of the particles, which is now square. The basic difference of these two systems lies in the interaction: hard core elastic collisions make the dynamics of the disks chaotic whereas that of squares is not. Remarkably, this difference is not reflected in the transport properties of the two systems: simulations show that the diffusion coefficients, velocity correlations and response functions of the heavy impurity are in agreement with kinetic theory for both the chaotic and the non-chaotic model. The relaxation to equilibrium, however, is very sensitive to the kind of interaction. These observations are used to reconsider and discuss some issues connected to chaos, statistical mechanics and diffusion.
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 HIV-1 Protease. The predicted sites are found to correlate well with clinical data on resistance to FDA-appr
oved 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 correlations suggests that the approach may be promisingly used in conjunction with traditional techniques to identify candidate locations for drug attacks.
Drug resistance to HIV-1 Protease involves accumulation of multiple mutations in the protein. Here we investigate the role of these mutations by using molecular dynamics simulations which exploit the influence of the native-state topology in the fold
ing process. Our calculations show that sites contributing to phenotypic resistance of FDA-approved drugs are among the most sensitive positions for the stability of partially folded states and should play a relevant role in the folding process. Furthermore, associations between amino acid sites mutating under drug treatment are shown to be statistically correlated. The striking correlation between clinical data and our calculations suggest a novel approach to the design of drugs tailored to bind regions crucial not only for protein function but also for folding.
