My research focuses on the thermodynamics and statistical mechanics of biomolecules, addressed theoretically and through computer simulations.

Broadly speaking, the goal of my work is to understand and quantify the physical mechanisms underlying the function of biomolecules at increasing levels of complexity. These molecules include organic polymers, such as proteins and nucleic acid chains, and smaller organic molecules, such as drugs, hormones, neurotransmitters, and other chemical species. Their collective and cooperative interactions inside the cell are fundamental in living organisms. Understanding how these molecules interact with each other and with the surrounding medium is a basic goal of my research.

Specifically, my work comprises three interrelated areas (click here for representative publications):

i) I am interested in understanding the physical principles underlying molecular association and dissociation in solutions. The aqueous medium controls virtually all properties of molecules in the cell, from chemical reactions of small molecules to the structure and thermodynamic of macromolecules. In particular, the solvent plays a critical role in the dynamics of molecular encounters and association/dissociation mechanisms, ultimately controlling the kinetics of biochemical pathways, macromolecular complexation and aggregation.

A component of this research is the development of theoretical models that can be used as the basis for computationally efficient methods. I am interested in developing methods for describing biomolecular interactions at the microscopic (atomistic), mesoscopic and macroscopic (thermodynamic) levels. The long-term goal of this work is to be able to connect the different levels of description in a unified picture, thus providing for a smooth transition between different length scales and time regimes, which in biology span several orders of magnitude. I use atomistic computer simulations to better understand the underlying forces operating on these systems, and use such computer experiments to guide the theoretical developments (read more).

ii) Application of computational methods (including Monte Carlo and Molecular Dynamics simulations) to specific problems of biological interest. I use classical molecular mechanics (MM) force fields and quantum mechanics/molecular mechanics (QM/MM) techniques. MM methods are used to study the thermodynamic of macromolecules, and QM/MM to study problems where a higher level of theory is needed to describe chemical reactions.

iii) Understanding the physical basis of self-organization and pattern formation in nonequilibrium, many-body systems. More specifically, I am interested in the microscopic origin (i.e., at the level of individual units) of macroscopic organization and formation of spatial and temporal structures. My main interest is to understand how biological systems self-organize. This is a basic question that concerns many systems in nature, not only in biology. However, in biology its relevance spans a broad spectrum of phenomena, ranging from complex molecular processes, e.g., the self-assembly of virus capsids, to macroscopic cellular processes, e.g., those involved in the cell cycle, to events at the level of organisms, to natural selection and evolution of species. Read more