Large-amplitude bending motions in phenylalanine transfer RNA.
TL;DR: These energies are comparable to those that would be associated with changes in solvation due to changes in surface area as the molecule bends, indicating that there are no major steric barriers to tRNA flexibility and that variations in solvent conditions and interactions with other molecules may produce large changes in the overall conformation of tRNA.
Abstract: Conformational energy calculations on yeast tRNAPhe reveal several likely modes of intramolecular bending, including both hingelike motions (rotations about a discrete point) and distributed flexibility (deformations that bend a double-helical segment along a smooth curve). By combining these modes of motion, the molecule can be bent from the L-shaped crystallographic structure to two extremes. It can be straightened into a nearly linear conformation at an energy cost of about 50 kcal/mol, and it can be doubled over to a conformation where the anticodon and the amino acid acceptor terminus are separated by about 40 A at an energy cost of less than 100 kcal/mol. A bending range of over 100° can be covered for 50 kcal/mol, and we estimate that this value could be cut in half with a minimization algorithm that produced optimum stereochemistry. These energies are comparable to those that would be associated with changes in solvation due to changes in surface area as the molecule bends, indicating that there are no major steric barriers to tRNA flexibility and that variations in solvent conditions and interactions with other molecules may produce large changes in the overall conformation of tRNA.
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TL;DR: In this paper, the mean squared positions and velocities of a harmonic oscillator are derived for Langevin dynamics algorithms valid in the high and low friction limits, and for the Verlet algorithm.
Abstract: Analytic expressions for mean squared positions and velocities of a harmonic oscillator are derived for Langevin dynamics algorithms valid in the high and low friction limits, and for the Verlet algorithm. For typical values of the parameters, errors in the positions are small. However, if the velocity is defined by the usual Verlet form, kinetic energies (and therefore calculated temperatures) can be in error by several per cent for the Langevin algorithms. If the Bunger-Brooks-Karplus algorithm is used to calculate positions, a simple redefinition of the velocity results greatly in improved kinetic energies. In addition, due to cancellation of errors in the velocities and the positions, the correct virial is obtained. The effect of including the force derivative in diffusive algorithms is examined. Positional and velocity averages are calculated for the Verlet algorithm for arbitrary initial conditions, and errors in the total energy and virial are analysed. Connection is made with the Langevin algorith...
834 citations
TL;DR: This system attempts to describe a protein motion as a rigid-body rotation of a small 'core' relative to a larger one, using a set of hinges, and finds that while this model can accommodate most protein motions, it cannot accommodate all; the degree to which a motion can be accommodated provides an aid in classifying it.
Abstract: The number of solved structures of macromolecules that have the same fold and thus exhibit some degree of conformational variability is rapidly increasing. It is consequently advantageous to develop a standardized terminology for describing this variability and automated systems for processing protein structures in different conformations. We have developed such a system as a ‘front-end’ server to our database of macromolecular motions. Our system attempts to describe a protein motion as a rigid-body rotation of a small ‘core’ relative to a larger one, using a set of hinges. The motion is placed in a standardized coordinate system so that all statistics between any two motions are directly comparable. We find that while this model can accommodate most protein motions, it cannot accommodate all; the degree to which a motion can be accommodated provides an aid in classifying it. Furthermore, we perform an adiabatic mapping (a restrained interpolation) between every two conformations. This gives some indication of the extent of the energetic barriers that need to be surmounted in the motion, and as a by-product results in a ‘morph movie’. We make these movies available over the Web to aid in visualization. Many instances of conformational variability occur between proteins with somewhat different sequences. We can accommodate these differences in a rough fashion, generating an ‘evolutionary morph’. Users have already submitted hundreds of examples of protein motions to our server, producing a comprehensive set of statistics. So far the statistics show that the median submitted motion has a rotation of ~10° and a maximum Cα displacement of 17 A. Almost all involve at least one large torsion angle change of >140°. The server is accessible at http://bioinfo.mbb.yale.edu/MolMovDB
259 citations
TL;DR: The vibrational dynamics of transfer RNAs, both free, and complexed with the cognate synthetase, are analyzed using a model (Gaussian network model) which recently proved to satisfactorily describe the collective motions of folded proteins.
136 citations
Cites methods from "Large-amplitude bending motions in ..."
...Tung et al. (1984) calculated the energy costs of deforming the tRNA with respect to different hinge regions using an adiabatic mapping method (McCammon & Harvey, 1987), and observed that the bending with respect to a hinge at the phosphates P8 and P49 costs less energy than at other sites....
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TL;DR: The increasing number of X‐ray structures of free, protein‐ and ribosome‐bound tRNA, reveal structural details accounting for the identity of the 22 tRNA families and for the multifunctionality of a given family, and the structural role of post‐transcriptional tRNA modifications is being deciphered.
Abstract: Transfer RNAs (tRNAs) are ancient molecules whose origin goes back to the beginning of life on Earth. Key partners in the ribosome-translation machinery, tRNAs read genetic information on messenger RNA and deliver codon specified amino acids attached to their distal 3'-extremity for peptide bond synthesis on the ribosome. In addition to this universal function, tRNAs participate in a wealth of other biological processes and undergo intricate maturation events. Our understanding of tRNA biology has been mainly phenomenological, but ongoing progress in structural biology is giving a robust physico-chemical basis that explains many facets of tRNA functions. Advanced sequence analysis of tRNA genes and their RNA transcripts have uncovered rules that underly tRNA 2D folding and 3D L-shaped architecture, as well as provided clues about their evolution. The increasing number of X-ray structures of free, protein- and ribosome-bound tRNA, reveal structural details accounting for the identity of the 22 tRNA families (one for each proteinogenic amino acid) and for the multifunctionality of a given family. Importantly, the structural role of post-transcriptional tRNA modifications is being deciphered. On the other hand, the plasticity of tRNA structure during function has been illustrated using a variety of technical approaches that allow dynamical insights. The large range of structural properties not only allows tRNAs to be the key actors of translation, but also sustain a diversity of unrelated functions from which only a few have already been pinpointed. Many surprises can still be expected.
133 citations
TL;DR: In this paper, it was shown that micromolar concentrations of a deprotonated aqueous complex of the lanthanide metal ion terbium(III), Tb(OH)(aq) 2a, reversibly inhibit the hairpin ribozyme by competing for a crucial, yet non-selective cation binding site.
90 citations
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TL;DR: The structure of a tRNA has been determined by isomorphous replacement but the interactions which maintain the tertiary structure are of a novel type and this model differs significantly from one which has recently been proposed.
Abstract: The structure of a tRNA has been determined by isomorphous replacement. Some of the interactions which maintain the tertiary structure are of a novel type. Our model differs significantly from one which has recently been proposed.
901 citations
TL;DR: A theoretical study of a low frequency vibration involving the two globular lobes of lysozyme between which the cleft containing the active site is located and finds that any motion involving this cleft could play a part in the catalytic activity.
Abstract: A COMPLETE description of an enzyme requires a knowledge of its structure and the dynamics of its function. From the crystal structures of enzymes and enzyme–inhibitor complexes and the known chemistry of model systems, it has been possible in some cases to draw reasonable inferences concerning the mechanisms of enzyme-catalysed reactions. Little has been done so far, however, to supplement such essentially static results by an investigation of the reaction dynamics. This requires an understanding of the internal motions of the enzyme, as well as those of the substrate, since both are likely to be essential to the function. Here we present a theoretical study of a low frequency vibration involving the two globular lobes of lysozyme between which the cleft containing the active site is located1. Any motion involving this cleft could play a part in the catalytic activity; in fact, atom displacements of up to 0.75 A found in a comparison of the free enzyme and the enzyme-inhibitor complex indicate that the cleft has closed down in the latter2. The force constant for the low frequency bending vibration corresponding to the opening and closing of the cleft is obtained from empirical energy functions3. Because the protein surface moves appreciably during the vibration, damping effects resulting from the viscous dissipation in the solvent are included in the calculation4,5.
345 citations
TL;DR: A dynamical analysis of the orientation fluctuations of two tyrosine side chains in the bovine pancreatic trypsin inhibitor is presented and it is found that the Langevin equation is applicable to the ring torsional motion, which corresponds to that of an angular harmonic oscillator with near-critical damping.
Abstract: To probe the details of small amplitude motions in proteins, a dynamical analysis of the orientation fluctuations of two tyrosine side chains in the bovine pancreatic trypsin inhibitor is presented. Detailed results are given for the time history and correlation functions obtained for the ring motion from a molecular dynamics simulation of the entire protein. It is shown that even on a picosecond time scale orientational fluctuations of +/-30 degrees from the average position occur for the tyrosine rings in the interior of the protein. It is found that the Langevin equation is applicable to the ring torsional motion, which corresponds to that of an angular harmonic oscillator with near-critical damping. Two possible microscopic models for the observed damping effects are outlined. One of these, analogous to liquid behavior, is based on kinetic theory and takes account of the collisions which occur between atoms of the protein; the other, more analogous to solid behavior, involves the coupling among a large number of harmonic oscillators. The collisional model with parameters obtained from theoretical estimates leads to good agreement with the correlation functions from the dynamic simulation. However, the dephasing of harmonic oscillations can yield similar short-time results so that a distinction between the two models is difficult. The importance of damping effects on the motions involved in conformational transitions and enzymatic reactions is discussed.
306 citations
TL;DR: The crystal structure of yeast tRNA Phe is refined at 2·5A resolution, using real-space refinement and improved electron density maps to confirm almost all the structural details found earlier by fitting a wire model to the map in an optical comparator.
273 citations
TL;DR: Theoretical conformational energy calculations show that large changes in the width of the binding-site cleft in the L-arabinose-binding protein involve only modestChanges in the protein internal energy.
253 citations