Marco Aurélio A. Barbosa

Non‐native interactions, effective contact order, and protein folding: A mutational investigation with the energetically frustrated hydrophobic model

By Monte Carlo simulations, we explored the effect of single mutations on the thermodynamics and kinetics of the folding of a two‐dimensional, energetically frustrated, hydrophobic protein model. Φ‐Value analysis, corroborated by simulations beginning from given sets of judiciously chosen initial contacts, suggests that the transition state of the model consists of a limited region of the native structure, that is, a folding nucleus. It seems that the most important contacts in the transition state (large and positive Φ) are not the ones with the highest contact order, because in this case the entropic cost of their formation would be too high, but exactly the ones that decrease the entropic cost of difficult contacts, reducing their effective contact order. Mutations of internal monomers involved in high‐order contacts were actually the ones resulting in the fastest kinetics (and Φ < 0), indicating they tend to make low order, non‐native contacts of low entropic cost that stabilize the unfolded state with respect to the transition state. Folding acceleration by other non‐native interactions was also observed and a simple general mechanism is proposed according to which non‐native contacts can act indirectly over the folding nucleus, “chelating” out potentially harmful contacts. The polymer graph of our model, which facilitates the visualization of effective contact orders, successfully suggests the relative kinetic importance of different contacts and is reasonably consistent with analogous graphs for the well characterized family of SH3 domains. Proteins 2002;49:167–180.

Multiple liquid-liquid critical points and density anomaly in core-softened potentials

The relation between liquid-liquid phase transitions and waterlike density anomalies in core-softened potentials of fluids was investigated in an exactly solvable one dimensional lattice model and a in a three dimensional fluid with fermi-like potential, the latter by molecular dynamics. Both systems were shown to present three liquid phases, two liquid-liquid phase transitions closely connected to two distinct regions of anomalous density increase. We propose that an oscillatory behavior observed on the thermal expansion coefficient as a function of pressure can be used as a signature of the connection between liquid-liquid phase and density.

Solution of an associating lattice-gas model with density anomaly on a Husimi lattice.

We study a model of a lattice gas with orientational degrees of freedom which resemble the formation of hydrogen bonds between the molecules. In this model, which is the simplified version of the Henriques-Barbosa model, no distinction is made between donors and acceptors in the bonding arms. We solve the model in the grand-canonical ensemble on a Husimi lattice built with hexagonal plaquettes with a central site. The ground state of the model, which was originally defined on the triangular lattice, is exactly reproduced by the solution on this Husimi lattice. In the phase diagram, one gas and two liquid [high density liquid (HDL) and low density liquid (LDL)] phases are present. All phase transitions (GAS-LDL, GAS-HDL, and LDL-HDL) are discontinuous, and the three phases coexist at a triple point. A line of temperatures of maximum density in the isobars is found in the metastable GAS phase, as well as another line of temperatures of minimum density appears in the LDL phase, part of it in the stable region and another in the metastable region of this phase. These findings are at variance with simulational results for the same model on the triangular lattice, which suggested a phase diagram with two critical points. However, our results show very good quantitative agreement with the simulations, both for the coexistence loci and the densities of particles and of hydrogen bonds. We discuss the comparison of the simulations with our results.

Residual entropy and waterlike anomalies in the repulsive one dimensional lattice gas

The thermodynamics and kinetics of the one dimensional lattice gas with repulsive interaction are investigated using transfer matrix technique and Monte Carlo simulations. This simple model is shown to exhibit waterlike anomalies in density, thermal expansion coefficient, and self-diffusion. An unified description for the thermodynamic anomalies in this model is achieved based on the ground state residual entropy which appears in the model due to mixing entropy in a ground state phase transition.