458 research outputs found
Multiplexed-Replica Exchange Molecular Dynamics with the UNRES Force-Field as an Effective Method for Exploring the Conformational Energy Landscape of Proteins.
Molecular dynamics simulations of the temperature-induced unfolding of crambin follow the Arrhenius equation
Molecular dynamics simulations have been used extensively to model the folding and unfolding of proteins. The rates of folding and unfolding should follow the Arrhenius equation over a limited range of temperatures. This study shows that molecular dynamic simulations of the unfolding of crambin between 500K and 560K do follow the Arrhenius equation. They also show that while there is a large amount of variation between the simulations the average values for the rate show a very high degree of correlation
The physics of pulling polyproteins: a review of single molecule force spectroscopy using the AFM to study protein unfolding
Cold Inactivation of l-Threonine Deaminase from Rhodospirillum rubrum
Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66171/1/j.1432-1033.1971.tb01491.x.pd
Analysis and Application of Potential Energy Smoothing and Search Methods for Global Optimization
Climate policy and ancillary benefits : a survey and integration into the modelling of international negotiations on climate change
Currently informal and formal international negotiations on climate change take place in an intensive way since the Kyoto Protocol expires already in 2012. A post-Kyoto regulation to combat global warming is not yet stipulated. Due to rapidly increasing greenhouse gas emission levels, industrialized countries urge major polluters from the developing world like China and India to participate in a future agreement. Whether these developing countries will do so, depends on the prevailing incentives to participate in international climate protection efforts. This paper identifies ancillary benefits of climate policy to provide important incentives to attend a new international protocol and to positively affect the likelihood of accomplishing a post-Kyoto agreement which includes commitments of developing countries
Hydrodynamic modelling of protein conformation in solution: ELLIPS and HYDRO
The last three decades has seen some important
advances in our ability to represent the conformation of
proteins in solution on the basis of hydrodynamic measurements.
Advances in theoretical modeling capabilities have
been matched by commensurate advances in the precision of
hydrodynamic measurements. We consider the advances in
whole-body (simple ellipsoid-based) modeling—still useful
for providing an overall idea of molecular shape, particularly
for those systems where only a limited amount of data is
available—and outline the ELLIPS suite of algorithms
which facilitates the use of this approach. We then focus
on bead modeling strategies, particularly the surface or
shell–bead approaches and the HYDRO suite of algorithms.
We demonstrate how these are providing great insights into
complex issues such as the conformation of immunoglobulins
and other multi-domain complexes
The Extended Cleavage Specificity of Human Thrombin
Thrombin is one of the most extensively studied of all proteases. Its central role in the coagulation cascade as well as several other areas has been thoroughly documented. Despite this, its consensus cleavage site has never been determined in detail. Here we have determined its extended substrate recognition profile using phage-display technology. The consensus recognition sequence was identified as, P2-Pro, P1-Arg, P1′-Ser/Ala/Gly/Thr, P2′-not acidic and P3′-Arg. Our analysis also identifies an important role for a P3′-arginine in thrombin substrates lacking a P2-proline. In order to study kinetics of this cooperative or additive effect we developed a system for insertion of various pre-selected cleavable sequences in a linker region between two thioredoxin molecules. Using this system we show that mutations of P2-Pro and P3′-Arg lead to an approximate 20-fold and 14-fold reduction, respectively in the rate of cleavage. Mutating both Pro and Arg results in a drop in cleavage of 200–400 times, which highlights the importance of these two positions for maximal substrate cleavage. Interestingly, no natural substrates display the obtained consensus sequence but represent sequences that show only 1–30% of the optimal cleavage rate for thrombin. This clearly indicates that maximal cleavage, excluding the help of exosite interactions, is not always desired, which may instead cause problems with dysregulated coagulation. It is likely exosite cooperativity has a central role in determining the specificity and rate of cleavage of many of these in vivo substrates. Major effects on cleavage efficiency were also observed for residues as far away as 4 amino acids from the cleavage site. Insertion of an aspartic acid in position P4 resulted in a drop in cleavage by a factor of almost 20 times
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