Research
Our overarching goal is to explore and understand biomolecules in solution using computer simulations. We seek to understand how the dynamics of biological macromolecules (proteins and nucleic acids) influences structure/function relationship across multiple time and length scales. To address these questions, we use molecular dynamics simulations and develop methods to extend the scope of the field in terms of what is possible to study using computer simulation. Our work is rooted in statistical mechanics, free energy calculations, and enhanced sampling methods.
Current topics of interest include: (i) developing computational methods and strategies to rapidly screen mutations for how they affect enzyme kinetic rates and reaction mechanisms, (ii) elucidating the seeding and fibril growth mechanism of the microtubule associated tau protein, linked to a number of dementias known as tauopathies that includes Alzheimer’s disease, (iii), understanding from a physical chemistry perspective the general driving forces of protein aggregation and liquid-liquid phase separation of intrinsically disordered proteins, and (iv) advancing new algorithms aimed at efficiently sampling protein conformational changes related to allosteric regulation.
Because of the hierarchical nature of biology, we use a number of computational methods to target different time and length scales ranging from the quantum regime up to the mesoscopic scale. At the highest resolution, ab initio molecular dynamics within the Born-Oppenheimer approximation can provide insight into chemical reaction mechanisms. At the molecular level, classical force fields speed up the calculation, enabling us to simulate large biomolecules in solution. Both methods are complemented by enhanced sampling methods such as metadynamics to more efficiently explore the system’s energy landscape. At lower resolution, we can consider grouping atoms together into coarse-grained effective interaction sites that can be studied by conventional molecular dynamics or by transformation into a polymer field theory.
For more details about our research, check out some of our recent publications.
