Publications
133 results found
De Simone A, Gianni S, Vendruscolo M, 2013, Structure of a Misfolded Intermediate of a PDZ Domain, Bio-nanoimaging: Protein Misfolding and Aggregation, Pages: 463-474, ISBN: 9780123944313
The process by which proteins fold into their native states generally involves the transient population of partially structured intermediate states. Determining the structures of these states is important not only in order to understand the molecular mechanisms leading to the formation of native states but also to elucidate the initial events by which proteins misfold and aggregate. By using a combination of kinetic, protein engineering, biophysical and computational techniques we have recently determined the structure of a misfolded intermediate of a PDZ domain and shown that this state is characterized by an alternative packing of the N-terminal β-hairpin onto an otherwise native-like scaffold. The non-native region in the misfolded intermediate includes residues that, in the native state, are involved in ligand binding, thus suggesting that folding and function might represent conflicting constraints on the folding process. These results indicate that the transient formation of misfolded compact states may involve the incorrect assembly of specific non-native elements within an overall native-like topology. © 2014 Elsevier Inc. All rights reserved.
Esposito L, Balasco N, De Simone A, et al., 2013, Interplay between Peptide Bond Geometrical Parameters in Nonglobular Structural Contexts, BIOMED RESEARCH INTERNATIONAL, Vol: 2013, ISSN: 2314-6133
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- Citations: 13
Peoc'h K, Levavasseur E, Delmont E, et al., 2012, Substitutions at residue 211 in the prion protein drive a switch between CJD and GSS syndrome, a new mechanism governing inherited neurodegenerative disorders, HUMAN MOLECULAR GENETICS, Vol: 21, Pages: 5417-5428, ISSN: 0964-6906
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- Citations: 21
Berisio R, Ciccarelli L, Squeglia F, et al., 2012, Structural and Dynamic Properties of Incomplete Immunoglobulin-like Fold Domains, PROTEIN AND PEPTIDE LETTERS, Vol: 19, Pages: 1045-1053, ISSN: 0929-8665
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- Citations: 8
Biedermann F, Uzunova VD, Scherman OA, et al., 2012, Release of High-Energy Water as an Essential Driving Force for the High-Affinity Binding of Cucurbit[<i>n</i>]urils, JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, Vol: 134, Pages: 15318-15323, ISSN: 0002-7863
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- Citations: 399
De Simone A, Stanzione F, Marasco D, et al., 2012, The intrinsic stability of the human prion β-sheet region investigated by molecular dynamics., J Biomol Struct Dyn
Human prion diseases are neurodegenerative disorders associated to the misfolding of the prion protein (PrP). Common features of prion disorders are the fibrillar amyloid deposits and the formation of prefibrillar oligomeric species also suggested as the origin of cytotoxicity associated with diseases. Although the process of PrP misfolding has been extensively investigated, many crucial aspects of this process remain unclear. We have here carried out a molecular dynamics study to evaluate the intrinsic dynamics of PrP β-sheet, a region that is believed to play a crucial role in prion aggregation. Moreover, as this region mediates protein association in dimeric assemblies frequently observed in prion crystallographic investigations, we also analyzed the dynamics of these intermolecular interactions. The extensive sampling of replica exchange shows that the native antiparallel β-structure of the prion is endowed with a remarkable stability. Therefore, upon unfolding, the persistence of a structured β-region may seed molecular association and influence the subsequent phases of the aggregation process. The analysis of the four-stranded β-sheet detected in the dimeric assemblies of PrP shows a tendency of this region to form dynamical structured states. The impact on the β-sheet structure and dynamics of disease associated point mutations has also been evaluated.
Montalvao RW, De Simone A, Vendruscolo M, 2012, Determination of structural fluctuations of proteins from structure-based calculations of residual dipolar couplings, JOURNAL OF BIOMOLECULAR NMR, Vol: 53, Pages: 281-292, ISSN: 0925-2738
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- Citations: 47
Stanzione F, De Simone A, Esposito L, et al., 2012, Dynamical Properties of Steric Zipper Polymorphs Formed by a IAPP-Derived Peptide, PROTEIN AND PEPTIDE LETTERS, Vol: 19, Pages: 846-851, ISSN: 0929-8665
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- Citations: 1
Knowles TJP, De Simone A, Fitzpatrick A, et al., 2012, Twisting transition between crystalline and fibrillar phases of aggregated peptides, Physical Review Letters
We study two distinctly ordered condensed phases of polypeptide molecules, amyloid fibrils and amyloid-like microcrystals, and the first-order twisting phase transition between these two states. We derive a single free-energy form which connects both phases. Our model identifies relevant degrees of freedom for describing collective behaviour of supra-molecular polypeptide structures, reproduces accurately the results from molecular dynamics simulations as well as from experiments, and sheds light on the uniform nature of the dimensions of different peptide fibrils.
Bemporad F, De Simone A, Chiti F, et al., 2012, Characterizing Intermolecular Interactions That Initiate Native-Like Protein Aggregation, BIOPHYSICAL JOURNAL, Vol: 102, Pages: 2595-2604, ISSN: 0006-3495
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- Citations: 23
Kuehrova P, De Simone A, Otyepka M, et al., 2012, Force-Field Dependence of Chignolin Folding and Misfolding: Comparison with Experiment and Redesign, BIOPHYSICAL JOURNAL, Vol: 102, Pages: 1897-1906, ISSN: 0006-3495
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- Citations: 64
Fusco G, De Simone A, Hsu S-TD, et al., 2012, <SUP>1</SUP>H, <SUP>13</SUP>C and <SUP>15</SUP>N resonance assignments of human muscle acylphosphatase, BIOMOLECULAR NMR ASSIGNMENTS, Vol: 6, Pages: 27-29, ISSN: 1874-2718
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- Citations: 14
Camilloni C, De Simone A, Vranken WF, et al., 2012, Determination of Secondary Structure Populations in Disordered States of Proteins Using Nuclear Magnetic Resonance Chemical Shifts, BIOCHEMISTRY, Vol: 51, Pages: 2224-2231, ISSN: 0006-2960
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- Citations: 263
Camilloni C, Robustelli P, De Simone A, et al., 2012, Characterization of the Conformational Equilibrium between the Two Major Substates of RNase A Using NMR Chemical Shifts., J Am Chem Soc, Vol: 134, Pages: 3968-3971
Following the recognition that NMR chemical shifts can be used for protein structure determination, rapid advances have recently been made in methods for extending this strategy for proteins and protein complexes of increasing size and complexity. A remaining major challenge is to develop approaches to exploit the information contained in the chemical shifts about conformational fluctuations in native states of proteins. In this work we show that it is possible to determine an ensemble of conformations representing the free energy surface of RNase A using chemical shifts as replica-averaged restraints in molecular dynamics simulations. Analysis of this surface indicates that chemical shifts can be used to characterize the conformational equilibrium between the two major substates of this protein.
Camilloni C, Schaal D, Schweimer K, et al., 2012, Energy Landscape of the Prion Protein Helix 1 Probed by Metadynamics and NMR, BIOPHYSICAL JOURNAL, Vol: 102, Pages: 158-167, ISSN: 0006-3495
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- Citations: 38
De Simone A, Kitchen C, Kwan A, et al., 2012, Intrinsic Disorder Modulates Protein Self-Assembly and Aggregation, Proc Natl Acad Sci U S A, Vol: 109, Pages: 6951-6956
De Simone A, Dhulesia A, Soldi G, et al., 2011, Experimental free energy surfaces reveal the mechanisms of maintenance of protein solubility, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, Vol: 108, Pages: 21057-21062, ISSN: 0027-8424
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- Citations: 57
De Simone A, Montalvao RW, Vendruscolo M, 2011, Determination of Conformational Equilibria in Proteins Using Residual Dipolar Couplings, JOURNAL OF CHEMICAL THEORY AND COMPUTATION, Vol: 7, Pages: 4189-4195, ISSN: 1549-9618
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- Citations: 35
Vitagliano L, Berisio R, De Simone A, 2011, Role of Hydration in Collagen Recognition by Bacterial Adhesins, BIOPHYSICAL JOURNAL, Vol: 100, Pages: 2253-2261, ISSN: 0006-3495
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- Citations: 22
Masino L, Nicastro G, De Simone A, et al., 2011, The Josephin Domain Determines the Morphological and Mechanical Properties of Ataxin-3 Fibrils, BIOPHYSICAL JOURNAL, Vol: 100, Pages: 2033-2042, ISSN: 0006-3495
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- Citations: 39
Gianni S, Ivarsson Y, De Simone A, et al., 2010, Structural characterization of a misfolded intermediate populated during the folding process of a PDZ domain, NATURE STRUCTURAL & MOLECULAR BIOLOGY, Vol: 17, Pages: 1431-U57, ISSN: 1545-9993
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- Citations: 45
De Simone A, Derreumaux P, 2010, Low molecular weight oligomers of amyloid peptides display β-barrel conformations: A replica exchange molecular dynamics study in explicit solvent, JOURNAL OF CHEMICAL PHYSICS, Vol: 132, ISSN: 0021-9606
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- Citations: 49
Nicastro G, Masino L, Esposito V, et al., 2009, Josephin Domain of Ataxin-3 Contains Two Distinct Ubiquitin-Binding Sites, BIOPOLYMERS, Vol: 91, Pages: 1203-1214, ISSN: 0006-3525
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- Citations: 71
Vitagliano L, Stanzione F, De Simone A, et al., 2009, Dynamics and Stability of Amyloid-Like Steric Zipper Assemblies with Hydrophobic Dry Interfaces, BIOPOLYMERS, Vol: 91, Pages: 1161-1171, ISSN: 0006-3525
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- Citations: 20
De Simone A, Cavalli A, Hsu S-TD, et al., 2009, Accurate Random Coil Chemical Shifts from an Analysis of Loop Regions in Native States of Proteins, JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, Vol: 131, Pages: 16332-+, ISSN: 0002-7863
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- Citations: 78
De Simone A, Richter B, Salvatella X, et al., 2009, Toward an Accurate Determination of Free Energy Landscapes in Solution States of Proteins, JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, Vol: 131, Pages: 3810-+, ISSN: 0002-7863
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- Citations: 61
Berisio R, De Simone A, Ruggiero A, et al., 2009, Role of side chains in collagen triple helix stabilization and partner recognition, JOURNAL OF PEPTIDE SCIENCE, Vol: 15, Pages: 131-140, ISSN: 1075-2617
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- Citations: 37
Vitagliano L, Esposito L, Pedone C, et al., 2008, Stability of single sheet GNNQQNY aggregates analyzed by replica exchange molecular dynamics: Antiparallel <i>versus</i> parallel association, BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, Vol: 377, Pages: 1036-1041, ISSN: 0006-291X
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- Citations: 28
De Simone A, Corrie JET, Dale RE, et al., 2008, Conformation and Dynamics of a Rhodamine Probe Attached at Two Sites on a Protein: Implications for Molecular Structure Determination <i>in situ</i>, JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, Vol: 130, Pages: 17120-17128, ISSN: 0002-7863
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- Citations: 9
De Simone A, Esposito L, Pedone C, et al., 2008, Insights into stability and toxicity of amyloid-like oligomers by replica exchange molecular dynamics analyses, BIOPHYSICAL JOURNAL, Vol: 95, Pages: 1965-1973, ISSN: 0006-3495
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- Citations: 48
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