Automatic Identification of Mobile and Rigid Substructures in Molecular Dynamics Simulations and Fractional Structural Fluctuation Analysis

Martı́nez, Leandro

doi:10.1371/journal.pone.0119264

Cited by 350 publications

(190 citation statements)

References 20 publications

(36 reference statements)

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“…Mean square root of the deviation (RMSD) trajectory analysis for GTF and GTF‐V systems was carried out using the mdlovofit program. This program makes a robust alignment of the structures by means of low‐order‐value‐optimization, identifying the mobile regions in each frame, in order to iteratively obtain an optimized alignment.…”

Section: Methodsmentioning

confidence: 99%

“…Mean square root of the deviation (RMSD) trajectory analysis for GTF and GTF-V systems was carried out using the mdlovofit 20 Mechanics/Molecular Mechanics (QM/MM) approaches. 21,22 A different result was obtained for a protein region located in the neighborhood of the catalytic site, namely the α4 0 -loop-α4 00 motif, which has been recognized as a relevant segment for GTF-SI activity.…”

Section: Trajectory Analysismentioning

confidence: 99%

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Modulation of glucan‐enzyme interactions by domain V in GTF‐SI from Streptococcus mutans

et al. 2018

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Glucansucrase GTF‐SI from Streptococcus mutans is a multidomain enzyme that catalyzes the synthesis of glucan polymers. Domain V locates 100 Å from the catalytic site and is required for an optimal activity. Nevertheless, the mechanism governing its functional role remains elusive. In this work, homology modeling and molecular dynamics simulations were employed to examine the effect of domain V in the structure and glucan‐binding ability of GTF‐SI in full and truncated enzyme models. Our results showed that domain V increases the flexibility of the α4′‐loop‐α4″ motif near the catalytic site resulting in a higher surface for glucan association, and modulates the orientation of a growing oligosaccharide (N=8‐23) in glucan‐enzyme complexes towards engaging in favorable contacts throughout the protein, whereas in the truncated model the glucan protrudes randomly from domain B towards the solvent. These results are valuable to increase understanding about the functional role of domain V in GH70 glucansucrases.

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Section: Methodsmentioning

confidence: 99%

Section: Trajectory Analysismentioning

confidence: 99%

Modulation of glucan‐enzyme interactions by domain V in GTF‐SI from Streptococcus mutans

et al. 2018

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“…To explore the situation in the cleavage reaction, all-atom MD simulations of these OCVs were carried out. The structural stability of the cleavage sequence was evaluated via the root-mean-square fluctuations (RMSF) for Cα atoms from the 10-ns simulation trajectory files [30]. The RMSF values for the cleavage sequences of the three variants are shown in Figure 5A.…”

Section: Discussionmentioning

confidence: 99%

Study on Cecropin B2 Production via Construct Bearing Intein Oligopeptide Cleavage Variants

Fang

et al. 2020

Molecules

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In this study, genetic engineering was applied to the overexpression of the antimicrobial peptide (AMP) cecropin B2 (cecB2). pTWIN1 vector with a chitin-binding domain (CBD) and an auto-cleavage Ssp DnaB intein (INT) was coupled to the cecB2 to form a fusion protein construct and expressed via Escherichia coli ER2566. The cecB2 was obtained via the INT cleavage reaction, which was highly related to its adjacent amino acids. Three oligopeptide cleavage variants (OCVs), i.e., GRA, CRA, and SRA, were used as the inserts located at the C-terminus of the INT to facilitate the cleavage reaction. SRA showed the most efficient performance in accelerating the INT self-cleavage reaction. In addition, in order to treat the INT as a biocatalyst, a first-order rate equation was applied to fit the INT cleavage reaction. A possible inference was proposed for the INT cleavage promotion with varied OCVs using a molecular dynamics (MD) simulation. The production and purification via the CBD-INT-SRA-cecB2 fusion protein resulted in a cecB2 yield of 58.7 mg/L with antimicrobial activity.

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“…The last 50 ns of production dynamics were analyzed in order to retrieve structural and energetic information regarding the association of PLA, LAU, TX, and PLA‐TX to reduced MT models. Trajectory alignment, root‐mean‐square deviation (RMSD), and root‐mean‐square fluctuation (RMSF) calculations for Cα atoms were carried out using MDLovoFit functionalities . Cutoff distances of 3.0 and 4.0 Å, were employed to identify hydrogen bonds, and salt bridges, respectively, with a hydrogen bond angle cutoff of 20° using VMD software implementations.…”

Section: Methodsmentioning

confidence: 99%

“…Trajectory alignment, root-mean-square deviation (RMSD), and root-mean-square fluctuation (RMSF) calculations for Cα atoms were carried out using MDLovoFit functionalities. 26 Cutoff distances of 3.0 and 4.0 Å, were employed to identify hydrogen bonds, and salt bridges, respectively, with a hydrogen bond angle cutoff of 20 using VMD software implementations. 16 MM/GBSA binding free energy calculations 27 were employed to estimate the strength of dimer-dimer interactions in MT models in ligand-free and ligand-bonded states treating the α 1 β 1 dimer as one monomer, and the α 2 β 2 dimer as the second monomer.…”

Section: Trajectory Analysismentioning

confidence: 99%

Molecular modeling study on the differential microtubule‐stabilizing effect in singly‐ and doubly‐bonded complexes with peloruside A and paclitaxel

et al. 2019

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Microtubules (MT) are dynamic cytoskeletal components that play a crucial role in cell division. Disrupting MT dynamics by MT stabilizers is a widely employed strategy to control cell proliferation in cancer therapy. Most MT stabilizers bind to the taxol (TX) site located at the luminal interface between protofilaments, except laulimalide and peloruside A (PLA), which bind to an interfacial pocket on outer MT surface. Cryo‐electron microscopy MTs reconstructions have shown differential structural effects on the MT lattice in singly‐ and doubly‐bonded complexes with PLA, TX, and PLA/TX, as PLA is able to revert the lattice heterogeneity induced by TX association leading to more regular MT assemblies. In this work, fully‐atomistic molecular dynamics simulations were employed to examine the single and double association of MT stabilizers to reduced MT models in the search for structural and energetic evidence that could be related to the differential regularization and stabilization effects exerted by PLA and TX on the MT lattice. Our results revealed that the double association of PLA/TX (a) strengthens the lateral contact between tubulin dimers compared to singly‐bonded complexes, (b) favors a more parallel arrangement between tubulin dimers, and (c) induces a larger restriction in the interdimeric conformational motion increasing the probability of finding structures consistent with 13‐protofilaments arrangements. These results and are valuable to increase understanding about the molecular mechanism of action of MT stabilizers, and could account for an overstabilization of MTs in doubly‐bonded complexes compared to singly‐bonded systems.

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Automatic Identification of Mobile and Rigid Substructures in Molecular Dynamics Simulations and Fractional Structural Fluctuation Analysis

Cited by 350 publications

References 20 publications

Modulation of glucan‐enzyme interactions by domain V in GTF‐SI from Streptococcus mutans

Modulation of glucan‐enzyme interactions by domain V in GTF‐SI from Streptococcus mutans

Study on Cecropin B2 Production via Construct Bearing Intein Oligopeptide Cleavage Variants

Molecular modeling study on the differential microtubule‐stabilizing effect in singly‐ and doubly‐bonded complexes with peloruside A and paclitaxel

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