Research overview

We are interested in questions related to molecular mechanisms in biomolecular processes. In particular, we are interested in exploring physical principles governing the conformational transitions of proteins and nucleic acids. How do proteins fold? Do all proteins adopt unique three-dimensional structures? What are the energetic and entropic determinants for preferred folding pathways? How do environmental factors influence the folding pathways and intermediate states?

In recent years, misfolded proteins and structured aggregates have been implicated in a class of disorders, such as Alzheimer’s, Parkinson’s and mad cow diseases, underscoring the need for molecular- and atomic-level understanding of protein folding. While advances in protein engineering and other experimental techniques have been leading the way in mapping folding pathways of proteins, significant progress has also been made in theoretical investigations. Notably, the folding funnel theory has enabled theoretical predictions of protein folding pathways using native-state based coarse-grained models. High performance computing power combined with implicit solvent models and advanced conformational sampling methods have allowed in silico folding of small proteins at atomic resolution.

Guided by classical, statistical and quantum mechanical theories, we are developing theoretical methods and physical models, and implementing them into computer simulations to elucidate molecular mechanisms in biological processes. Some of our current projects include metal-ion binding to proteins; pH effects in protein folding and amyloid formation; conformational dynamics of RNA; methods for accelerated molecular simulations.

News

Oct 23, 2007 - Dr. Khandogin's recent work on Alzheimer's beta amyloid peptides was highlighted in the Alzheimer Research Forum and the News & Views of the Scripps Research Institute.