Hybrid Voronoi diagrams, their computation and reduction for applications in computational biochemistry

Maňák, Martin; Zemek, Michal; Szkandera, Jakub; Kolingerová, Ivana; Papaleo, Elena; Lambrughi, Matteo

doi:10.1016/j.jmgm.2017.03.018

Cited by 6 publications

(5 citation statements)

References 22 publications

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“…For example, although eukaryotic ribosomes are generally larger in size than bacterial ones, their exit tunnel is narrower with heterogeneous variations along it [ 14 , 98 ]. Various algorithms and computational methods adapted to molecular structures, based on tesselation [ 99 , 100 , 101 ] (illustrated in Figure 4 a), or spectral geometry [ 102 ], can be used to encode the structure into geometric objects [ 103 ], and in particular compare ribosome geometric features. For example, by estimating the relative position of residues to the surface, one can separate proteins according to their degree of exposition to the solvent (see Figure 4 b), which has been hypothesized as a key factor for differentiating proteins prone to ribosome repair [ 64 ] or with distinct electrostatic properties [ 104 ].…”

Section: Computational Challenges For Quantifying Heterogeneity Frmentioning

confidence: 99%

Structural Heterogeneities of the Ribosome: New Frontiers and Opportunities for Cryo-EM

Poitevin

Kushner

et al. 2020

Molecules

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The extent of ribosomal heterogeneity has caught increasing interest over the past few years, as recent studies have highlighted the presence of structural variations of the ribosome. More precisely, the heterogeneity of the ribosome covers multiple scales, including the dynamical aspects of ribosomal motion at the single particle level, specialization at the cellular and subcellular scale, or evolutionary differences across species. Upon solving the ribosome atomic structure at medium to high resolution, cryogenic electron microscopy (cryo-EM) has enabled investigating all these forms of heterogeneity. In this review, we present some recent advances in quantifying ribosome heterogeneity, with a focus on the conformational and evolutionary variations of the ribosome and their functional implications. These efforts highlight the need for new computational methods and comparative tools, to comprehensively model the continuous conformational transition pathways of the ribosome, as well as its evolution. While developing these methods presents some important challenges, it also provides an opportunity to extend our interpretation and usage of cryo-EM data, which would more generally benefit the study of molecular dynamics and evolution of proteins and other complexes.

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Section: Computational Challenges For Quantifying Heterogeneity Frmentioning

confidence: 99%

Structural Heterogeneities of the Ribosome: New Frontiers and Opportunities for Cryo-EM

Poitevin

Kushner

et al. 2020

Molecules

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“…In particular, we selected two set of parameters. The first set aimed to monitor the evolution of solvent-accessible tunnels from the protein surface towards the catalytic site, where we used a probe radius of 1.5 Å, comparable to the size of a water molecule [73], a shell radius of 5 Å, shell depth of 4 Å, and a clustering threshold of 7 Å. In the second set of parameters, we used the same parameters as the first set but with a probe radius of 2.0 Å to resemble the size of the natural substrate 3-methylaspartate.…”

Section: Methodsmentioning

confidence: 99%

Conformational gating in ammonia lyases

Lambrughi

Maršić

Sáez-Jiménez

et al. 2019

Preprint

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14Ammonia lyases (AL) are enzymes of industrial and biomedical interest. Knowledge 15 of AL structure-dynamics-function relationship would be instrumental for making use 16 of the application potential of these enzymes. We investigated, using microsecond 17 molecular dynamics, the conformational changes in the proximity of the catalytic 18 pocket of a 3-methylaspartate ammonia lyase (MAL) as a model system. In 19 particular, we identified two regulatory elements in the MAL structure, i.e., the β 5-α2 20 loop, and the helix-hairpin-loop subdomain. We showed that they undergo 21 conformational changes switching from 'occluded' to 'open' states. We observed that 22 these rearrangements are coupled to changes in the accessibility of the active site. 23 The β 5-α2 loop and the helix-hairpin-loop subdomain modulate the formation of 24 tunnels from the protein surface to the substrate binding site, making the active site 25 more accessible to the substrate when they are in an open state. We pinpointed a 26 sequential mechanism, in which the helix-hairpin-loop subdomain needs to break a 27 subset of intramolecular interactions first, to then allow the opening of the β 5-α2 loop 28 and, as a consequence, make the AL catalytic pocket accessible for the substrate.29 2 Our data suggest that protein dynamics need to be considered in the design of new 1 AL variants for protein engineering and therapeutic purposes. 2 Keywords 3 molecular dynamics simulations, conformational changes, disordered regions, 4 conformational switches, correlated motions 5 6

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“…The first set aimed to monitor the evolution of solvent-accessible tunnels from the protein surface towards the catalytic site, where we used a probe radius of 1.5 Å, comparable to the size of a water molecule [73], a shell radius of 5 Å, shell depth of 4 Å, and a clustering threshold of 7 Å. In the second set of parameters, we used the same parameters as the first set but with a probe radius of 2.0 Å to resemble the size of the natural substrate 3-methylaspartate.…”

Section: Tunnel Analysesmentioning

confidence: 99%

Conformational gating in ammonia lyases

Lambrughi

Maršić

Sáez-Jiménez

et al. 2020

Biochimica et Biophysica Acta (BBA) - General Subjects

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Ammonia lyases (AL) are enzymes of industrial and biomedical interest. Knowledge of AL structure-dynamics-function relationship would be instrumental for making use of the application potential of these enzymes. We investigated, using microsecond molecular dynamics, the conformational changes in the proximity of the catalytic pocket of a 3-methylaspartate ammonia lyase (MAL) as a model system. In particular, we identified two regulatory elements in the MAL structure, i.e., the Our data suggest that protein dynamics need to be considered in the design of new AL variants for protein engineering and therapeutic purposes.

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Hybrid Voronoi diagrams, their computation and reduction for applications in computational biochemistry

Cited by 6 publications

References 22 publications

Structural Heterogeneities of the Ribosome: New Frontiers and Opportunities for Cryo-EM

Structural Heterogeneities of the Ribosome: New Frontiers and Opportunities for Cryo-EM

Conformational gating in ammonia lyases

Conformational gating in ammonia lyases

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