Folding speed limit

Chang I-J, Lee JC, Winkler JR, Gray HB. The protein-folding speed limit Intrachain diffusion times set by electron-transfer rates in denatured Ru(NH3)5(His-33)-Zii-cytochrome c. Proc Natl Acad Sci USA 2003 100 3838-40. 

J. Kubelka, J. Hofrichter, W. A. Eaton (2004) The protein folding speed limit . (Turr. Opin. Struc. Biol. 14, pp. 76-88... 

Bieri, O., Wirz, J., Hellrung, B., Schutkowski, M., Drewello, M., Kiefhaber, T., The Speed Limit for Protein Folding Measured by Triplet Triplet Energy Transfer, Proc. Natl. Acad. Sci. USA 1999, 96, 9597 9601. 

Ensign, D. L., Kasson, P. M., 8c Pande, V. S. (2007). Heterogeneity even at the speed limit of folding Large-scale molecular dynamics study of a fastfolding variant of the villin headpiece. Journal of Molecular Biology, 374, 806. 

D. L. Ensign, P. M. Kasson, and V. S. Pande,/. Mol. Biol., 374, 806 (2007). Heterogeneity Even at the Speed Limit of Folding Large-Scale Molecular Dynamics Study of a Fast-Folding Variant of the Villin Headpiece. 

Most successful is a rotating Pt wire microelectrode as illustrated in Fig. 3.75 as a consequence of the rotation, which should be of a constant speed, the steady state is quickly attained and the diffusion layer thickness appreciably reduced, thus raising the limiting current (proportional to the rotation speed to the 1/3 power above 200 rpm140 and 15-20-fold in comparison with a dme) and as a result considerably improving the sensitivity of the amperometric- titration. 

How well has Dill s prediction held up In 2000, the first ever microsecond-long molecular dynamics simulation of protein folding was reported. It required 750,000 node hours (equal to the product of the number of hours times the number of processors) of computer time on a Cray T3 supercomputer. According to Dill s prediction, this length of simulation was not to be expected until around 2010. However, as noted above, Dill s analysis does not take into account large-scale parallelization—which, unless the computation is communications-limited, will effectively increase the speed of a computation in proportion to the number of processors available. 

The basic difference between an common FTIR spectrometer and a FTIR imaging spectrometer consists in the layout of the detector. The FPA of the imaging spectrometer is made of the same material (MCT) as detectors of common FTIR spectrometers, it only houses 4096 individual detector elements arranged in a 64 x 64 array. This results in a 4096-fold increase in spectral data amount. Speed of data transfer and time needed for evaluation of thousands of spectra are current the limiting factors to capture and to evaluate FTIR images. A semi-quantitative display of time fractions during measurement of FTIR images is shown in Fig. 3. 

The use of perfusion colunms (Ch. 1.4.1) was also evaluated to speed up the LC separation of proteins prior to ESI-MS [49]. Five-fold faster analysis was reported. Due to the narrow chromatographic peaks (5-10 s), the number of protein mass spectra available for transformation is limited. 

To avoid diffusional limitations it is advisable to assay the enzyme activity under more drastic conditions. Amongst other things, this means increasing stirrer speed to exclude external diffusion, crushing the particles to reduce porous diffusion, increasing the substrate concentration to about > 100-fold of K vi-value to avoid lack of substrate at the center of the particles or adding buffer to avoid pH-shifts. If the reaction rate is increased by any of these means it is likely that diffusional control is operative and can to some extent be reduced or even eliminated. 

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