1. The Chong Group Computational Molecular Biophysics Molecular switches
Natively unfolded proteins
unfolded proteins fold only upon binding
At least a third of the proteins in five different organisms are predicted to be natively unfolded (Dunker et al., 1999)
An increasing number of proteins are natively unfolded, or ‘intrinsically unstructured’ (Wright and Dyson, 1999)
Many proteins can be turned on or off via induced conformational change
Conformational changes may be caused by binding other molecules or due to environmental changes
Group members (from the left): Ranqi Zhu (G), Brandon Mills (U), Monica Bhattacharjee (U), Lillian Chong (PI), John Sekar (G), and Om Choudhary (G).
Research interests
What could “unfolded” mean?
Induced unfolding
In a two-domain protein, the folding of one subunit can be used to drive the unfolding of another, and vice versa (Loh et al., 2003)
By using the induced unfolding paradigm, new molecular switches may be engineered that have the functionality of natural proteins with added selectivity
The central goal of the Chong lab is to use theory and simulation to understand how proteins fold, bind their partners, and catalyze reactions, with an emphasis on how malfunctions at the molecular level can be linked to clinical data for various diseases. To achieve this goal, we develop accurate approaches for simulation and subsequent analysis of protein structure and function.
Fully disordered, i.e. random coil
Mostly disordered with local regions of structure
Structured only part of the time
The project
Tumor suppressor p53
The barnase/ubiquitin chimera
In collaboration with Vijay Pande’s Group at Stanford: More than 250,000 volunteers world-wide have downloaded the screen saver client, running parts of our simulations during their idle computing time. To join, go to
July, 2002 PDB molecule of the month by DS Goodsell
We are using computer simulations to study the structure and dynamics of p53’s natively unfolded domains. More than half of all cancers are linked to malfunctions of p53.
We are studying the barnase/ubiquitin chimera as a model for induced unfolding.