Browsing by Author "Celeste Sagui, Committee Chair"

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Evaluating Free Energies in Different Scale Systems: Chemical Reactions and Nanopatterns.
(2006-07-21) Asciutto, Eliana Karina; Celeste Sagui, Committee Chair
All the thermodynamical properties of a given system can be obtained from the knowledge of the free energy of such system and its derivatives. Thus, a study of different methods to evaluate free energies is of considerable importance for physical, chemical and biological systems. However, free energy calculations are not straightforward in practice. For chemical systems for example, the complication is mainly due to the difficulty of calculating the entropy of the system. In order to overcome this difficulty, special methodologies have been introduced to provide some tools in the estimation of relative free energies for molecular systems via computer simulations. Another example where free energy calculations are challenging is the physics of phase transitions, i.e. the boiling of a liquid, the transition from paramagnetic to ferromagnetic behavior of a metal, etc. This thesis is divided in two parts. In the first part, the evaluation of free energy differences in chemical reactions is investigated through a novel method developed by Laio et al called Metadynamics(1). This method not only allows for the evaluation of free energy differences but also accelerates the reactions, driving the system through high free energy barriers and sampling regions of low probability. As an application, two important carboxylic acids, malonic and formic acid, were studied and their structure, energetics, intramolecular reactions and solvent interactions were determined. The deprotonation of the formic acid in presence of water was also fully investigated. In the second part, phase transition phenomena are considered, using the phenomenological Laundau-Ginsburg-Wilson Free Energy Functional. We investigated self-assembled domain patterns of modulated systems. They appear as a result of competing short-range attractive and long-range repulsive interasystems. From an application point of view, there is considerable interest in this domain patterns, as they form templates suitable for the fabrication of nanostructures. We have generated a variety of new and exotic patterns, which represent either metastable or glassy states. These patterns arise as a compromise between the required equilibrium modulation period and the strain resulting from topologically constrained trajectories in phase space that effectively preclude the equilibrium configuration.
Towards Predictive Molecular Dynamics Simulations of DNA: Role of Electrostatics and of the Cell Environment.
(2007-01-11) Baucom, Jason Butler; Celeste Sagui, Committee Chair; Christopher Roland, Committee Member; Carla Mattos, Committee Member; Steffen Heber, Committee Member
Molecular dynamics simulations of the DNA duplex d(CCAACGTTGG)2 were used to study the relationship between DNA sequence and structure in a crystal environment. Three different force fields were used: a traditional description based on atomic point charges, a polarizable force field, and an "extra-point" force field (with additional charges on extranuclear sites). It is found that all the force fields reproduce fairly well the sequence-dependent features of the experimental structure. The polarizable force field, however, provides the most accurate representation of the crystal structure and the sequence-dependent effects observed in the experiment. These results point out to the need of the inclusion of polarization for accurate descriptions of DNA. This work has also investigated to what extent molecular dynamics (MD) simulations can reproduce DNA sequence-specific features, given different electrostatic descriptions and different cell environments. For this purpose, we have carried out multiple unrestrained MD simulations of the DNA duplex d(CCAACGTTGG)2. With respect to the electrostatic descriptions, two different force fields are studied: a traditional description based on atomic point charges and a polarizable force field. With respect to the cell environment, the difference between crystal and solution environments is emphasized, as well as the structural importance of divalent ions. By imposing the correct experimental unit cell environment, an initial configuration with two ideal B-DNA duplexes in the unit cell, is shown to converge to the crystallographic structure. This convergence is measured by the appearance of sequence-dependent features that very closely resemble the crystallographic ones, as well as by the decay of the all-atom root-mean-squared coordinates deviations (RMSD) with respect to the crystallographic structure. Given the appropriate crystallographic constraints, this is first example of multiple nanosecond molecular dynamics trajectory that shows an ideal B-DNA model converging to an experimental structure, with a significant decay of RMSD. At later times, the polarizable force field is able to maintain this lower RMSD while the nonpolarizable force field starts to drift away.