Faculty Profiles - TAMA Florence

Papers - TAMA Florence

Division display 101 - 111 of about 111 ／ All the affair displays >>

Ribosome motions modulate electrostatic properties Reviewed

J Trylska, R Konecny, F Tama, CL Brooks, JA McCammon

BIOPOLYMERS Vol. 74 ( 6 ) page： 423 - 431 2004.8

Language：English Publishing type：Research paper (scientific journal) Publisher：WILEY-BLACKWELL

The electrostatic properties of the 70S ribosome of Thermus thermophilus were studied qualitatively by solving the Poisson-Boltzmann (PB) equation in aqueous solution and with physiological ionic strength. The electrostatic potential was calculated for conformations of the ribosome derived by recent normal mode analysis (Tama, F., et al. Proc Natl Acad Sci USA 2003 1001, 9319-9323) of the ratchet-like reorganization that occurs during translocation (Frank, J.; Agrawal, R. K. Nature 2000 406, 318-322). To solve the PB equation, effective parameters (charges and radii), applicable to a highly charged backbone model of the ribosome, were developed. Regions of positive potential were found at the binding site of the elongation factors G and Tu, as well as where the release factors bind. Large positive potential areas are especially pronounced around the L11 and L6 proteins. The region around the L1 protein is also positively charged, supporting the idea that L1 may interact with the E-site tRNA during its release from the ribosome after translocation. Functional rearrangement of the ribosome leads to electrostatic changes which may help the translocation of the tRNAs during the elongation stage. (C) 2004 Wiley Periodicals, Inc.

DOI： 10.1002/bip.20093

Web of Science

Flexible multi-scale fitting of atomic structures into low-resolution electron density maps with elastic network normal mode analysis Reviewed

F Tama, O Miyashita, CL Brooks

JOURNAL OF MOLECULAR BIOLOGY Vol. 337 ( 4 ) page： 985 - 999 2004.4

Language：English Publishing type：Research paper (scientific journal) Publisher：ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD

A novel method is presented for the quantitative flexible docking of high-resolution structure into low-resolution maps of macromolecular complexes from electron microscopy. This method uses a linear combination of low-frequency normal modes from elastic network description of the molecular framework in an iterative manner to deform the structure optimally to conform to the low-resolution electron density map. The methodology utilizes gradient following techniques in collective normal modes to locally optimize the overall correlation coefficient between computed and measured electron density. To evaluate the performance of our approach, several proteins, which undergo large conformational changes, have been studied. We demonstrate that refinement based on normal mode analysis provides an accurate and fast alternative for the flexible fitting of high-resolution structure into a low-resolution density map. Additionally, we show that lower resolution (multi-scale) structural models can be used for the normal mode searching in lieu of fully atomic models with little loss of overall accuracy. (C) 2004 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.jmb.2004.01.048

Web of Science

Topology representing neural networks reconcile biomolecular shape, structure, and dynamics Reviewed

W Wriggers, P Chacon, JA Kovacs, F Tama, S Birmanns

NEUROCOMPUTING Vol. 56 page： 365 - 379 2004.1

Language：English Publishing type：Research paper (scientific journal) Publisher：ELSEVIER SCIENCE BV

Topology-representing networks (TRNs) generate reduced models of biomolecules and thereby facilitate the fitting of molecular fragments into large macromolecular complexes. The components of such complexes undergo a wide range of motions, and shapes observed at low resolution often deviate from the known atomic structures. What is required for the modeling of such motions is a combination of global shape constraints based on the low-resolution data with a local modeling of atomic interactions. We present a novel Motion Capture Network that freezes inessential degrees of freedom to maintain the stereochemistry of an atomic model. TRN-based deformable models retain much of the mechanical properties of biological macromolecules. The elastic models yield a decomposition of the predicted motion into vibrational normal modes and are amenable to interactive manipulation with haptic rendering software. (C) 2003 Elsevier B.V. All rights reserved.

DOI： 10.1016/j.neucom.2003.09.007

Web of Science

Dynamic reorganization of the functionally active ribosome explored by normal mode analysis and cryo-electron microscopy Reviewed Open Access

F Tama, M Valle, J Frank, CL Brooks

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Vol. 100 ( 16 ) page： 9319 - 9323 2003.8

Language：English Publishing type：Research paper (scientific journal) Publisher：NATL ACAD SCIENCES

Combining structural data for the ribosome from x-ray crystallography and cryo-electron microscopy with dynamic models based on elastic network normal mode analysis, an atomically detailed picture of functionally important structural rearrangements that occur during translocation is elucidated. The dynamic model provides a near-atomic description of the ratchet-like rearrangement of the 70S ribosome seen in cryo-electron microscopy, and permits the identification of bridging interactions that either facilitate the conformational switching or maintain structural integrity of the 50S/30S interface. Motions of the tRNAs residing in the A and P sites also suggest the early stages of tRNA translocation as a result of this ratchet-like movement. Displacement of the L1 stalk, alternately closing and opening the intersubunit space near the E site, is observed in the dynamic model, in line with growing experimental evidence for the role of this structural component in facilitating the exiting of tRNA. Finally, a hinge-like transition in the 30S ribosomal subunit, similar to that observed in crystal structures of this complex, is also manifest as a dynamic mode of the ribosome. The coincidence of these dynamic transitions with the individual normal modes of the ribosome and the good correspondence between these motions and those observed in experiment suggest an underlying principle of nature to exploit the shape of molecular assemblies such as the ribosome to provide robustness to functionally important motions.

DOI： 10.1073/pnas.1632476100

Open Access

Web of Science

Normal mode analysis with simplified models to investigate the global dynamics of biological systems Reviewed

F Tama

PROTEIN AND PEPTIDE LETTERS Vol. 10 ( 2 ) page： 119 - 132 2003.4

Language：English Publisher：BENTHAM SCIENCE PUBL LTD

Dynamical properties of macromolecules are increasingly being recognized as significantly contributing to biological functions, including catalysis, regulation of activity, etc. In this review, theoretical approaches to the study of dynamics of biological systems and their application are discussed. In particular, simplified models for the normal mode analysis are described.

DOI： 10.2174/0929866033479077

Web of Science

Mega-Dalton biomolecular motion captured from electron microscopy reconstructions Reviewed

P Chacon, F Tama, W Wriggers

JOURNAL OF MOLECULAR BIOLOGY Vol. 326 ( 2 ) page： 485 - 492 2003.2

Language：English Publishing type：Research paper (scientific journal) Publisher：ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD

The vibrational analysis of elastic models suggests that the essential motions of large biomolecular assemblies can be captured efficiently at an intermediate scale without requiring knowledge of the atomic structure. While prior work has established a theoretical foundation for this analysis, we demonstrate here on experimental electron microscopy maps that vibrational modes indeed describe functionally relevant movements of macromolecular machines. The clamp closure in bacterial RNA polymerase, the ratcheting of 30 S and 50 S subunits of the ribosome, and the dynamic flexibility of chaperonin CCT are extracted directly from single electron microscopy structures at 15-27 Angstrom resolution. The striking agreement of the presented results with experimentally observed motions suggests that the motion of the large scale machinery in the cell is surprisingly independent of detailed atomic interactions and can be quite reasonably described as a motion of elastic bodies. (C) 2003 Elsevier Science Ltd. All rights reserved.

DOI： 10.1016/S0022-2836(02)01426-2

Web of Science

Exploring global distortions of biological macromolecules and assemblies from low-resolution structural information and elastic network theory Reviewed

F Tama, W Wriggers, CL Brooks

JOURNAL OF MOLECULAR BIOLOGY Vol. 321 ( 2 ) page： 297 - 305 2002.8

Language：English Publishing type：Research paper (scientific journal) Publisher：ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD

A theory of elastic normal modes is described for the exploration of global distortions of biological structures and their assemblies based upon low-resolution image data. Structural information at low resolution, e.g. from density maps measured by cryogenic electron microscopy (cryo-EM), is used to construct discrete multi-resolution models for the electron density using the techniques of vector quantization. The elastic normal modes computed based on these discretized low-resolution models are found to compare well with the normal modes obtained at atomic resolution. The quality of the normal modes describing global displacements of the molecular system is found to depend on the resolution of the synthetic EM data and the extent of reductionism in the discretized representation. However, models that reproduce the functional rearrangements of our test set of molecules are achieved for realistic values of experimental resolution. Thus large conformational changes as occur during the functioning of biological macromolecules and assemblies can be elucidated directly from low-resolution structural data through the application of elastic normal mode theory and vector quantization. (C) 2002 Elsevier Science Ltd. All rights reserved.

DOI： 10.1016/S0022-2836(02)00627-7

Web of Science

The mechanism and pathway of pH induced swelling in cowpea chlorotic mottle virus Reviewed

F Tama, CL Brooks

JOURNAL OF MOLECULAR BIOLOGY Vol. 318 ( 3 ) page： 733 - 747 2002.5

Language：English Publishing type：Research paper (scientific journal) Publisher：ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD

Normal mode analysis based on a simplified energy function was used to study the swelling process of the icosahedral virus, cowpea chlorotic mottle virus (CCMV). Native state virus particles (coat proteins) of this T = 3 icosahedral virus have been shown to undergo a large conformational change to a swollen state when metal ions are removed or the pH is raised. A normal mode analysis based on the native state capsid showed one preferential direction, a breathing mode, that explains the majority of the structural rearrangement necessary to bring the native structure close to the swollen state.
From the native form of CCMV, the structure can be displaced along the direction of a single breathing mode by different amounts to create several candidate swollen structures and a putative pathway for virus expansion. The R-factor between these predicted swollen capsid structures and experimental electron density from cryoelectron microscopy (cryo-EM) measurements is then calculated to indicate how well each structure satisfies the experimental measurements on the swollen capsid state. A decrease of the crystallographic R-factor value from similar to72% to similar to49% was observed for these simple incremental displacements along the breathing mode. The simultaneous displacement of the native structure along other relevant (symmetric, non-degenerate) modes produce a structure with an R-factor of 45%, which is further reduced to 43.9% after minimization: a value in good accord with models based on the EM data at 28 Angstrom resolution.
Based on the incrementally expanded structures, a pathway for the swelling process has been proposed. Analysis of the intermediate structures along this pathway indicates a significant loss of interactions at the quasi-3-fold interfaces occurs in the initial stages of the swelling process and this serves as a trigger for the compact to swollen transition. Furthermore, the pH dependent swelling appears to be triggered by the titration of a single residue with an anomalous pK(a) value in the unswollen particle. (C) 2002 Elsevier Science Ltd. All rights reserved.

DOI： 10.1016/S0022-2836(02)00135-3

Web of Science

Conformational change of proteins arising from normal mode calculations Reviewed Open Access

F Tama, YH Sanejouand

PROTEIN ENGINEERING Vol. 14 ( 1 ) page： 1 - 6 2001.1

Language：English Publishing type：Research paper (scientific journal) Publisher：OXFORD UNIV PRESS

A normal mode analysis of 20 proteins in 'open' or 'closed' forms was performed using simple potential and protein models. The quality of the results was found to depend upon the form of the protein studied, normal modes obtained with the open form of a given protein comparing better with the conformational change than those obtained with the closed form. Moreover, when the motion of the protein is a highly collective one, then, in all cases considered, there is a single low-frequency normal mode whose direction compares well with the conformational change. When it is not, in most cases there is still a single low-frequency normal mode giving a good description of the pattern of the atomic displacements, as they are observed experimentally during the conformational change. Hence a lot of information on the nature of the conformational change of a protein is often found in a single low-frequency normal mode of its open form. Since this information can be obtained through the normal mode analysis of a model as simple as that used in the present study, it is likely that the property captured by such an analysis is for the most part a property of the shape of the protein itself. One of the points that has to be clarified now is whether or not amino acid sequences have been selected in order to allow proteins to follow a single normal mode direction, as least at the very beginning of their conformational change.

DOI： 10.1093/protein/14.1.1

Web of Science

Building-block approach for determining low-frequency normal modes of macromolecules Reviewed

F Tama, FX Gadea, O Marques, YH Sanejouand

PROTEINS-STRUCTURE FUNCTION AND GENETICS Vol. 41 ( 1 ) page： 1 - 7 2000.10

Language：English Publishing type：Research paper (scientific journal) Publisher：WILEY-LISS

Normal mode analysis of proteins of various sizes, ranging from 46 (crambin) up to 858 residues (dimeric citrate synthase) were performed, by using standard approaches, as well as a recently proposed method that rests on the hypothesis that low-frequency normal modes of proteins can be described as pure rigid-body motions of blocks of consecutive amino-acid residues. Such a hypothesis is strongly supported by our results, because we show that the latter method, named RTB, yields very accurate approximations for the low-frequency normal modes of all proteins considered. Moreover, the quality of the normal modes thus obtained depends very little on the way the polypeptidic chain is split into blocks, Noteworthy, with six aminoacids per block, the normal modes are almost as accurate as with a single amino-acid per block. In this case, for a protein of n residues and N atoms, the RTB method requires the diagonalization of an n x n matrix, whereas standard procedures require the diagonalization of a 3N x 3N matrix. Being a fast method, our approach can be useful for normal mode analyses of large systems, paving the way for further developments and applications in contexts for which the normal modes are needed frequently, as for example during molecular dynamics calculations. Proteins 2000;41:1-7. (C) 2000 Wiley-Liss, Inc.

Web of Science

Molecular dynamics simulation shows large volume fluctuations of proteins Reviewed

F Tama, O Miyashita, A Kitao, N Go

EUROPEAN BIOPHYSICS JOURNAL WITH BIOPHYSICS LETTERS Vol. 29 ( 7 ) page： 472 - 480 2000

Language：English Publishing type：Research paper (scientific journal) Publisher：SPRINGER-VERLAG

In this paper we present a new approach to study the volume fluctuations of proteins. From a 1 ns molecular dynamics simulation, the volume fluctuation of human lysozyme has been calculated. We used two different ways for the calculation. In the first one, the volume fluctuation is extracted directly from the trajectory. For the second one, a newly developed formalism based on principal component analysis is used. The r.m.s. volume fluctuations obtained from the two analyses agree well with each other. The isothermal intrinsic compressibility was found to be larger than the one reported by experiment. The difference is discussed and suggested to exist in the assumed uncertainty of the compressibility of hydrated water to deduce the isothermal intrinsic compressibility from the experimental value. Spectral analysis shows that low-frequency dynamics dominate the total volume fluctuation. The same aspect is found in the study using principal component analysis. This low-frequency region is related to large and slow motions of proteins. Therefore a long time dynamics simulation is necessary to describe the volume fluctuations of proteins.

DOI： 10.1007/s002490000103

Web of Science

　 PREV - NEXT 　

<TAMA Florence >

Papers - TAMA Florence