Motions Biological Function

Cyclophilin A (CypA) is a peptidyl-prolyl cis/trans isomerase that catalyzes the interconversion of X-Pro bonds. Conformational fluctuations of the active site of CypA that occur on a time scale of hundreds of microseconds 

The feex value (2730 s ) available from fitting and relaxation data is very close to the sum of the rate constants of and k c substrate isomerization on the enzyme (2500 s ). The microscopic chemical exchange rate, feex, of RNase A was found to be identical for all the mobile residues, located in the active site and substrate binding sites, with an average of 

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Conventional MS in the energy domain has contributed a lot to the understanding of the electronic ground state of iron centers in proteins and biomimetic models ([55], and references therein). However, the vibrational properties of these centers, which are thought to be related to their biological function, are much less studied. This is partly due to the fact that the vibrational states of the iron centers are masked by the vibrational states of the protein backbone and thus techniques such as Resonance Raman- or IR-spectroscopy do not provide a clear picture of the vibrational properties of these centers. A special feature of NIS is that it directly reveals the fraction of kinetic energy due to the Fe motion in a particular vibrational mode. 

Protein dynamics are extremely complex and difficult to analyze, because a variety of motions take place in the same molecule and at the same time. The key problem here is to determine which of these motions in a protein are essential for its biological function. In order to address this issue, we need detailed knowledge of protein dynamics. 

Very little is known about the motions of lipid bilayers at elevated pressures. Of particular interest would be the knowledge of the eifect of pressure on lateral diifusion, which is related to biological functions such as electron transport and some hormone-receptor interactions. However, pressure eifects on lateral diifusion of pure lipid molecules and of other membrane components have yet to be studied carefully. 

NMR is a powerful and versatile tool for structural studies of biological RNAs and complexes they form with other nucleic acids, proteins, and small molecules. The goal of these studies is to determine the role that structure and dynamics play in biological function. NMR has the capacity to determine high-resolution structures, as well as to map RNAiligand interfaces at low resolution. Most structures of RNA and RNA-ligand complexes are under 20 KDa in size however, recent advances allow for determination of solution structures of complexes up to 40 kDa. NMR can also probe dynamic motions in RNA on micro- to millisecond time scales. A number of biologically relevant internal motions such as... 

Another important application of NMR is concerned with the property of motional freedom to which many physical and biological functions of carbohydrates... 

One big issue of the post-Genome Project era is proteomics since proteins play crucial roles in virtually all biological processes such as enzymatic catalysis, coordinated motion, mechanical support, etc. [1]. A protein is a long polymer of amino acids, and folds into a regular structure for its biological function. 

Biomolecular recognition is mediated by water motions, and the dynamics of associated water directly determine local structural fluctuation of interacting partners [4, 9, 91]. The time scales of these interactions reflect their flexibility and adaptability. For water at protein surfaces, the studies of melittin and other proteins [45, 46] show water motions on tens of picoseconds. For trapped water in protein crevices or cavities, the dynamics becomes much slower and could extend to nanoseconds [40, 71, 92], These rigid water molecules are often hydrogen bonded to interior residues and become part of the structural integrity of many enzymes [92]. Here, we study local water motions in various environments, from a buried crevice to an exposed surface using site-selected tryptophan but with different protein conformations, to understand the correlation between hydration dynamics and conformational transitions and then relate them to biological function. 

All of the simulation approaches, other than harmonic dynamics, include the basic elements that we have outlined. They differ in the equations of motion that are solved (Newton s equations, Langevin equations, etc.), the specific treatment of the solvent, and/or the procedures used to take account of the time scale associated with a particular process of interest (molecular dynamics, activated dynamics, etc.). For example, the first application of molecular dynamics to proteins considered the molecule in vacuum.15 These calculations, while ignoring solvent effects, provided key insights into the important role of flexibility in biological function. Many of the results described in Chapts. VI-VIII were obtained from such vacuum simulations. Because of the importance of the solvent to the structure and other properties of biomolecules, much effort is now concentrated on systems in which the macromolecule is surrounded by solvent or other many-body environments, such as a crystal. 

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