Dynamics and flexibility

Proteins are known to exhibit internal motions over a time scale ranging from 10 second to greater than 1 second [187]. These motions include thermal vibrations (10 second), rotations of side chains about single bonds which are relatively 

Thermal vibrations of atoms which have a frequency of about 10 second are slow compared to the X-ray frequency, which is about 10 second . Consequently, the atoms appear to be stationary to the X-rays and the diffraction pattern represents a time average of many instantaneous states. If the motion of the atoms is harmonic so that the restoring force is proportional to the distance of the atom from its rest position and if the motion is isotropic so that the mean square displacements of the atom in all directions are the same, then is related to the temperature factor, B, by 

Displacements may arise not only from thermal motion but also from static disorder when corresponding atoms in different unit cells take up slightly different mean positions. Certain side chains, especially those exposed, may take up a few radically different conformations in different molecules so that separate images of them can be seen with reduced occupancy in electron density maps. The mean square displacement will also include contributions from lattice disorders but these are usually small in protein crystals that diffract well to high resolution [191]. In principle, the thermal vibrations can be distinguished from static disorder by varying temperature. Simple harmonic vibrations are expected to decrease linearly with temperature. 

There are certain practical aspects that need to be taken into account in assessing the significance of temperature factors. Errors in measurement of intensities, arising for example from incomplete correction of radiation damage or absorption, will have more serious effects on temperature factors than on atomic positions. The data must extend to a resolution of better than 2 A, otherwise temperature factors tend to be underestimated. Restraints in the refinement which assume that positional disorders of bonded atoms are highly correlated may bias the results. However, it is encouraging that in several structures (e.g., rubredoxin [193] and avian pancreatic polypeptide [194]) where the restraints were relaxed these assumptions were found to be valid. 

Displacements derived from temperature factors have been compared with those obtained from molecular dynamics. In these calculations, an empirical potential energy function is expressed as a function of the positional co-ordinates of the atoms. This function is then used to o,.. ain the force on each atom (energy is a generalised force X a generalised displacement) and the Newtonian equations of motion are solved for a small time interval, usually a fraction of a picosecond. Good agreement has been obtained for BPTI [195] and cytochrome c [196]. There are likely to be significant developments in this field as the sophistication of both refinement and simulation methods is increased. 

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In short, we return to C. P. Snow s recommendation that the scientist and humanist converse more. The conversations, analysis, and discussion should include the third culture, the technologist. Therefore, although we have not provided specihc and detailed analysis of issues related to computer use in the pharmaceutical industry, believing as we do that that sort of analysis is for the specialized philosopher doing conceptual analysis in computers ethics, we do urge that applied philosophers be part of the research team. Also, in the dynamic and flexible world of technology, applied philosophers—not just the people in the held of computers—should help draft policy statements and codes of conduct. 

The innate sensitivity of DNA-mediated CT to perturbations in the TT-stack has prompted us to employ this chemistry as a probe of stacking structure and dynamics. We have developed a new class of DNA-based diagnostic tools that diagnose DNA mutations such as single base-pair mismatches and lesions, analyze DNA-protein interactions, and probe the sequence-depen-dent dynamics and flexibility of DNA. These applications rely on electrochemical probing of CT in DNA films self-assembled on gold electrodes. 

However, even if you are using structures with the same sequence as the target sequence, you need to remember that these structures are also just models. In reality proteins are dynamic and flexible, and some parts of a protein are much more dynamic and flexible than others. These regions may be hinges, which allow secondary structure elements or entire domains to move relative to each other, or they may be loops that extend into the solution and can flip. Often, some of these movements are relevant to the function of the protein (e.g., the protein may have quite different structural states with or without a ligand). 

Wollman, F. A. 2001. State transitions reveal the dynamics and flexibility of the photosynthetic apparatus. EMBOJ. 20 3623-3630. 

U.S. negotiators realized that a total ban on ozone-depleting substances was neither justified by existing scientific knowledge nor politically feasible. Therefore, in place of the immutable commitments of traditional treaties, we deliberately drafted the protocol to constitute a dynamic and flexible process. The spirit of Montreal, which became a hallmark of later negotiations to strengthen the protocol, was to proceed incrementally in small, cumulative steps, rather than to reach for overambitious targets that would only serve to harden opposition. 

Such questions provoke heated debate in organic circles among both producers and consumers, and no doubt will continue to do so. With its continued growth, organic farming is constantly faced with new situations that need to be analyzed with appropriate attention to its fundamental principles and traditions on one hand, and the need to remain dynamic and flexible on the other. Any time it thinks it has the answer to the kinds of questions raised here, it s in trouble. 

Time-dependent nature of the technique provides information about the temporal (dynamic and flexibility) properties of a protein s structure (see Chapter 5)... 

Our belief that dynamics and flexibility are both retained in A-pivot lariat ether complexes derives from two sources. First, we have studied the relaxation times (Ti) for a variety of A-pivot lariat ethers using C-NMR [6]. The C-NMR results show essentially no change in the mobility of detectable nuclei whether or not the lariat ether is complexed by sodium or potassium cations. Second, ultrasound relaxation time studies conducted collaboratively with Petrucci and Eyring [13] have confirmed high binding rates for a two-step complexation mechanism. 

Protein Dynamics and Flexibility OrdCT and Disorder in Proteins. 304... 

The FCC process has been upgraded continuously since it was introduced in 1942. Two of the original three units built by Standard Oil of New Jersey at Baton Rouge, Louisiana, in 1942-1943 were still operating well after 1992. Combined production of PCLA 2 and 3 had been increased from 34,000 bpd of gas oil in 1943 to 188,000 bpd in 1992. PCLA 1 was dismantled in 1963 after expansion of the original 15,000 bpd capacity to 41,000 bpd. Many similar successful improvements have been made at other refineries. Table 5.15 shows how the developments in the FCC process and catalysts made this possible. It was a dynamic and flexible process. Further demands were made when reformulated gasoline was introduced, first in the United States and then in other parts of the world. 

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