Biomolecular force field development
Accurate force fields are vital for MD simulations to have real predictive power. Accordingly, force field development is one of the main thrusts of our research group. We have previously worked on the optimization of backbone torsion parameters and both solute-water and solute-solute van der Waals parameters using experimental data. More recently, working in collaboration with Prof. Lee-Ping Wang’s research group at UC Davis and the Open Force Field Initiative, we have developed water models, a new partial charge model for biomolecules, and a force field for phosphorylated amino acids.
We are currently working on new models for electrostatic interactions to be incorporated into next-generation classical force fields.
Post-translational modifications
Post-translational modifications (PTMs) are chemical modifications made to amino acids either during or after translation that can affect a protein’s structure and thermodynamics, as well as its interactions with other biomolecules. In addition to being important for regular physiological function, aberrant PTMs have been implicated in many diseases, ranging from various types of cancers to Alzheimer’s disease. As a PhD student I examined the effects of post-translational modifications in folded proteins, such as type I collagen and the small globular protein Im7. After gaining expertise in simulating intrinsically disordered peptides and proteins, my research group collaborated with Prof. Cecilia Zurita-Lopez at Chapman University to study how two adjacent PTMs in the histone H3 tail interact to modulate its function in gene transcription.
We are currently working on a project to understand how hyperphosphorylation of the intrinsically disordered tau protein alters its conformational ensemble and therefore may play a role in neurodegenerative diseases, including Alzheimer’s disease.