Macromolecular crowding modulates folding mechanism of alpha/beta protein apoflavodoxin

Protein dynamics in cells may be different from that in dilute solutions in vitro since the environment in cells is highly concentrated with other macromolecules. This volume exclusion due to macromolecular crowding is predicted to affect both equilibrium and kinetic processes involving protein conformational changes. To quantify macromolecular crowding effects on protein folding mechanisms, here we have investigated the folding energy landscape of an alpha/beta protein, apoflavodoxin, in the presence of inert macromolecular crowding agents using in silico and in vitro approaches. By coarse-grained molecular simulations and topology-based potential interactions, we probed the effects of increased volume fraction of crowding agents (phi_c) as well as of crowding agent geometry (sphere or spherocylinder) at high phi_c. Parallel kinetic folding experiments with purified Desulfovibro desulfuricans apoflavodoxin in vitro were performed in the presence of Ficoll (sphere) and Dextran (spherocylinder) synthetic crowding agents. In conclusion, we have identified in silico crowding conditions that best enhance protein stability and discovered that upon manipulation of the crowding conditions, folding routes experiencing topological frustrations can be either enhanced or relieved. The test-tube experiments confirmed that apoflavodoxin's time-resolved folding path is modulated by crowding agent geometry. We propose that macromolecular crowding effects may be a tool for manipulation of protein folding and function in living cells.Comment: to appear in Biophysical Journal (2009). to appear in Biophysical Journal (2009

Crowding out or crowding in?

Intergenerational support regains attention in course of population aging. This paper focuses on the relationship between private and public financial transfers to and from the elderly. Based on German data we find that the giving of private transfers is influenced by public transfers. The close link between public transfers to the elderly and the financial support they give to others represents an inefficient backflow of pay-as-you-go financed pensions to the young generation. This mechanism can be interpreted as a private compensation device for the generations. We can also show that at the same time the receipt of public transfers by the elderly crowd-out private financial support they would have received otherwise in the German welfare state.

Method to Predict Crowding Effects by Postprocessing Molecular Dynamics Trajectories: Application to the Flap Dynamics of HIV-1 Protease.

The internal dynamics of proteins inside of cells may be affected by the crowded intracellular environments. Here, we test a novel approach to simulations of crowding, in which simulations in the absence of crowders are postprocessed to predict crowding effects, against the direct approach of simulations in the presence of crowders. The effects of crowding on the flap dynamics of HIV-1 protease predicted by the postprocessing approach are found to agree well with those calculated by the direct approach. The postprocessing approach presents distinct advantages over the direct approach in terms of accuracy and speed and is expected to have broad impact on atomistic simulations of macromolecular crowding

On the theory of equalizing differences Increasing abundances of types of workers may increase their earnings

The theory of equalising differences recognises that wage differentials may be required to equalise the attractiveness of alternative occupations. We examine this theory using the Conley/Wooders 'crowding types'' model. The crowding types model distinguishes between the tastes of a player and his crowding type, those attributes of the player that directly effect the well-being of other players in the same club - a player''s skill, productivity or personality are examples. A club can be interpreted as firm in which the job attributes are the club goods thus, the crowding types model, with its distinction between tastes and crowding types, provides a natural environment in which to study equalising differences. In contrast to results for earlier models, we demonstrate that even when small groups of players are strictly effective in a strong sense, an increase in the abundance of players of one crowding type can increase the core payoffs to players of that crowding type.cooperative game theory

The Impact of Government Spending on the Private Sector: Crowding-out versus Crowding-in Effects"

The aim of this paper is to analyze the impact of government spending on the private sector, assessing the existence of crowding-out versus crowding-in effects. Using a panel of 145 countries from 1960 to 2007, the results suggest that government spending produces important crowding-out effects, by negatively affecting both private consumption and investment. Moreover, while the effects do not seem to depend on the different phases of economic cycle, they vary considerably among regions. The results are economically and statiscally significant, and robust to several econometic techniques.Fiscal Policy, Government Spending, Crowding-out, Crowding-in.

Public spending and Scottish devolution : crowding out, or crowding in?

There has been a developing debate about the performance of the Scottish economy under devolution and the effect of the expansion of the public sector on Scottish growth. Several commentators have expressed concern that the size of the public sector in Scotland is now a drag on growth, while others take a more sanguine view. This debate is well summarised in Marsh and Zuleeg (2006). However, this is a debate in which the evidence is often not well marshalled and there is often more heat than light generated. There is a suspicion that arguments about the effect and role of the public sector often derive more from the ultimate values and political preferences of proponents than from hard analysis and evidence

Crowding effects in vehicular traffic

While the impact of crowding on the diffusive transport of molecules within a cell is widely studied in biology, it has thus far been neglected in traffic systems where bulk behavior is the main concern. Here, we study the effects of crowding due to car density and driving fluctuations on the transport of vehicles. Using a microscopic model for traffic, we found that crowding can push car movement from a superballistic down to a subdiffusive state. The transition is also associated with a change in the shape of the probability distribution of positions from negatively-skewed normal to an exponential distribution. Moreover, crowding broadens the distribution of cars' trap times and cluster sizes. At steady state, the subdiffusive state persists only when there is a large variability in car speeds. We further relate our work to prior findings from random walk models of transport in cellular systems.Comment: 23 pages, 11 figures, accepted for publication in PLoS ON