The failure to appreciate that the hydration of polar groups is a major contribution to the entropy of protein unfolding has led to considerable underestimates for the loss of configurational freedom when a protein chain folds.

The long-held views on lock-and-key versus induced fit in binding arose from the notion that a protein exists in a single, most stable conformation, dictated by its sequence. However, in solution proteins exist in a range of conformations, which may be described by statistical mechanical laws and their populations follow statistical distributions. Upon binding, the equilibrium will shift in fav...

How the crowded environment inside cells affects folding, stability and structures of proteins is a vital question, since most proteins are made and function inside cells. Here we describe how crowded conditions can be created in vitro and in silico and how we have used this to probe effects on protein properties. We have found that folded forms of proteins become more compact in the presence o...

Recent successes show that, in certain circumstances, protein secondary structures can be predicted with high accuracy. How far are we from being able to predict the complete structure of a protein from its sequence?

Drugs that change the shape of AKT, a protein kinase that promotes tumor growth, may be more effective than drugs that only target its enzymatic activity.

Lattice models of proteins were used to examine the role of local propensities in stabilizing the native state of a protein, using techniques drawn from spin-glass theory to characterize the free-energy landscapes. In the strong evolutionary limit, optimal conditions for folding are achieved when the contributions from local interactions to the stability of the native state is small. Further in...

The early events in protein collapse and folding are guided by the protein's elasticity. The contributions of entropic coiling and poor solvent effects like hydrophobic forces to the elastic response of proteins are currently unknown. Using molecular simulations of stretched ubiquitin in comparison with models of proteins as entropic chains, we find a surprisingly high stiffness of the protein ...

Self-assembling cyclic protein homo-oligomers play important roles in biology, and the ability to generate custom homo-oligomeric structures could enable new approaches to probe biological function. Here we report a general approach to design cyclic homo-oligomers that employs a new residue-pair-transform method to assess the designability of a protein-protein interface. This method is sufficie...

Positive and negative feedback loops, for example, where a protein regulates its own transcription, play an important role in many genetic regulatory networks. Such systems will be subject to internal noise, which occurs due to the small number of molecules taking part in some reactions. This paper examines the effect of feedback loops on noise levels. Error growth techniques from nonlinear dyn...