iMod: multipurpose normal mode analysis in internal coordinates

López‐Blanco, José Ramón; Garzón, José Ignacio; Chacón, Pablo

doi:10.1093/bioinformatics/btr497

Cited by 223 publications

(198 citation statements)

References 55 publications

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“…All MD simulations analysed in this paper were extracted from the MoDEL database 39 , a large collection of atomistic trajectories for representative protein folds computed using state-of-the art standard protocols. High-frequency motions from MD simulations were filtered by PCA using pcatool, a development tool for the calibration of NMA calculations against MD and experimental structural ensembles 53 .…”

Section: Methodsmentioning

confidence: 99%

Correlated motions are a fundamental property of β-sheets

et al. 2014

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Correlated motions in proteins can mediate fundamental biochemical processes such as signal transduction and allostery. The mechanisms that underlie these processes remain largely unknown due mainly to limitations in their direct detection. Here, based on a detailed analysis of protein structures deposited in the protein data bank, as well as on state-of-the art molecular simulations, we provide general evidence for the transfer of structural information by correlated backbone motions, mediated by hydrogen bonds, across b-sheets. We also show that the observed local and long-range correlated motions are mediated by the collective motions of b-sheets and investigate their role in large-scale conformational changes. Correlated motions represent a fundamental property of b-sheets that contributes to protein function.

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Section: Methodsmentioning

confidence: 99%

Correlated motions are a fundamental property of β-sheets

et al. 2014

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“…Additional rigid and flexible body fitting was carried out for the empty CVA9-integrin ␣ v ␤ 6 density map. The capsid map containing the X-ray structure of CVA9 was zoned to a single asymmetric unit using the Zone feature in Chimera (47) with a zoning radius of 12 Å, followed by flexible fitting in iMODFIT (48) where all the dihedral angles were fixed and only rotation and translation of internal coordinates were allowed. The iMODFIT protocol was followed as described for dealing with huge systems on http://chaconlab.org /imodfit/faq.html.…”

Section: Methodsmentioning

confidence: 99%

Structural and Functional Analysis of Coxsackievirus A9 Integrin α _v β ₆ Binding and Uncoating

Shakeel

Seitsonen

Kajander

et al. 2013

J Virol

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bCoxsackievirus A9 (CVA9) is an important pathogen of the Picornaviridae family. It utilizes cellular receptors from the integrin ␣ v family for binding to its host cells prior to entry and genome release. Among the integrins tested, it has the highest affinity for ␣ v ␤ 6 , which recognizes the arginine-glycine-aspartic acid (RGD) loop present on the C terminus of viral capsid protein, VP1. As the atomic model of CVA9 lacks the RGD loop, we used surface plasmon resonance, electron cryo-microscopy, and image reconstruction to characterize the capsid-integrin interactions and the conformational changes on genome release. We show that the integrin binds to the capsid with nanomolar affinity and that the binding of integrin to the virion does not induce uncoating, thereby implying that further steps are required for release of the genome. Electron cryo-tomography and single-particle image reconstruction revealed variation in the number and conformation of the integrins bound to the capsid, with the integrin footprint mapping close to the predicted site for the exposed RGD loop on VP1. Comparison of empty and RNA-filled capsid reconstructions showed that the capsid undergoes conformational changes when the genome is released, so that the RNA-capsid interactions in the N termini of VP1 and VP4 are lost, VP4 is removed, and the capsid becomes more porous, as has been reported for poliovirus 1, human rhinovirus 2, enterovirus 71, and coxsackievirus A7. These results are important for understanding the structural basis of integrin binding to CVA9 and the molecular events leading to CVA9 cell entry and uncoating. Picornaviruses that belong to the Human enterovirus B species (HEV-B) in the family Picornaviridae are the major cause of aseptic meningitis (1, 2). HEV-B types, including coxsackievirus A9 (CVA9), also exhibit a wide range of other clinical manifestations of acute disease, including respiratory infections, myocarditis, encephalitis, paralysis, rash, and severe generalized infections in newborns (3-7). Moreover, there is evidence that suggests that HEV-B, specifically, CVA9, CVB1, CVB3, and CVB5, may be involved in the pathogenesis of childhood diabetes, the rate of incidence of which is increasing in Western countries (8-11).The CVA9 particle is about 28 nm in diameter and consists of a nonenveloped capsid with icosahedral symmetry, surrounding a positive-sense RNA genome of 7,452 nucleotides (12, 13). The CVA9 Tϭ1 (pseudo-Tϭ3) capsid is made up of 60 copies each of the four viral capsid proteins (VP1 to VP4) as revealed by its atomic model (12). Each of VP1, VP2, and VP3 possesses an eightstranded ␤-barrel structure. VP1 mainly forms the vertices of the capsid, with VP2 and VP3 alternating on the 3-fold and 2-fold axes of symmetry (12). These are common characteristics that are shared by most picornaviruses (12,14). Depressions of about 15 Å form the canyon region and are also seen around the 2-fold axes (12). CVA9 interacts with cell surface ␣ v integrins during the early stages of infection via an arginine-g...

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“…Concretely, iMod [9] is a tool chest that exploits the advantage of NMA formulations in internal coordinates (ICs) while extending them to cover multi-scale modeling. Despite the reduction in the degrees of freedom offered by ICs, the diagonalization step remains the major computational bottleneck of this approach, specially for large molecules.…”

Section: Introductionmentioning

confidence: 99%

Out-of-Core Solution of Eigenproblems for Macromolecular Simulations

Aliaga

Davidović

Quintana–Ort́ı

2014

Parallel Processing and Applied Mathematics

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Abstract. We consider the solution of large-scale eigenvalue problems that appear in the motion simulation of complex macromolecules on desktop platforms. To tackle the dimension of the matrices that are involved in these problems, we formulate out-of-core (OOC) variants of the two selected eigensolvers, that basically decouple the performance of the solver from the storage capacity. Furthermore, we contend with the high computational complexity of the solvers by off-loading the arithmeticallyintensive parts of the algorithms to a hardware graphics accelerator.

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iMod: multipurpose normal mode analysis in internal coordinates

Abstract: Supplementary data are available at Bioinformatics online.

Cited by 223 publications

References 55 publications

Correlated motions are a fundamental property of β-sheets

Correlated motions are a fundamental property of β-sheets

Structural and Functional Analysis of Coxsackievirus A9 Integrin α _v β ₆ Binding and Uncoating

Out-of-Core Solution of Eigenproblems for Macromolecular Simulations

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iMod: multipurpose normal mode analysis in internal coordinates

Abstract: Supplementary data are available at Bioinformatics online.

Cited by 223 publications

References 55 publications

Correlated motions are a fundamental property of β-sheets

Correlated motions are a fundamental property of β-sheets

Structural and Functional Analysis of Coxsackievirus A9 Integrin α v β 6 Binding and Uncoating

Out-of-Core Solution of Eigenproblems for Macromolecular Simulations

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Product

Resources

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Structural and Functional Analysis of Coxsackievirus A9 Integrin α _v β ₆ Binding and Uncoating