On the relationship between low-frequency normal modes and the large-scale conformational changes of proteins

Mahajan, Swapnil; Sanejouand, Yves‐Henri

doi:10.1016/j.abb.2014.12.020

Cited by 69 publications

(75 citation statements)

References 166 publications

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“…Residues that most contribute to the deformability of the system are indicated interaction between HSP70 and RAGE. The lowest modes are generally thought to dominantly contribute to the global and collective motions of the entire system (Bahar et al 2010;Mahajan and Sanejouand 2015).…”

Section: Resultsmentioning

confidence: 99%

Putative model for heat shock protein 70 complexation with receptor of advanced glycation end products through fluorescence proximity assays and normal mode analyses

Grunwald

Ligabue-Braun

Souza

et al. 2017

Cell Stress and Chaperones

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Extracellular heat shock protein 70 (HSP70) is recognized by receptors on the plasma membrane, such as Tolllike receptor 4 (TLR4), TLR2, CD14, and CD40. This leads to activation of nuclear factor-kappa B (NF-κB), release of proinflammatory cytokines, enhancement of the phagocytic activity of innate immune cells, and stimulation of antigenspecific responses. However, the specific characteristics of HSP70 binding are still unknown, and all HSP70 receptors have not yet been described. Putative models for HSP70 complexation to the receptor for advanced glycation endproducts (RAGEs), considering both ADP-and ATP-bound states of HSP70, were obtained through molecular docking and interaction energy calculations. This interaction was detected and visualized by a proximity fluorescence-based assay in A549 cells and further analyzed by normal mode analyses of the docking complexes. The interacting energy of the complexes showed that the most favored docking situation occurs between HSP70 ATP-bound and RAGE in its monomeric state. The fluorescence proximity assay presented a higher number of detected spots in the HSP70 ATP treatment, corroborating with the computational result. Normal-mode analyses showed no conformational deformability in the interacting interface of the complexes. Results were compared with previous findings in which oxidized HSP70 was shown to be responsible for the differential modulation of macrophage activation, which could result from a signaling pathway triggered by RAGE binding. Our data provide important insights into the characteristics of HSP70 binding and receptor interactions, as well as putative models with conserved residues on the interface area, which could be useful for future site-directed mutagenesis studies.

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Section: Resultsmentioning

confidence: 99%

Putative model for heat shock protein 70 complexation with receptor of advanced glycation end products through fluorescence proximity assays and normal mode analyses

Grunwald

Ligabue-Braun

Souza

et al. 2017

Cell Stress and Chaperones

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“…An alternate and promising approach to molecular dynamics is to infer dynamics from static structures corresponding to locally stable states (Mahajan and Sanejouand, 2015), together with reliable coarse-graining approaches to bridge the time-scale gap (Saunders and Voth, 2013; López-Blanco and Chacón, 2016). Cartesian Normal Modes, for example, represent a class of movements around a local energy minimum that are both straightforward to calculate and biologically relevant (Noguti and Go, 1982; Brooks et al, 1983; Levitt et al, 1985).…”

Section: Introductionmentioning

confidence: 99%

“…The Elastic Network Model (ENM), introduced by Tirion in 1996, offers a particularly simple and efficient way to calculate these modes, allowing fast access to the collective dynamics of large complexes with no minimization issues as it enforces that the crystal structure is already at the energy minimum (Tirion, 1996). This model was later expanded as the Gaussian Network Model (Bahar et al, 1997) and the Anisotropic Network Model (Hinsen, 1998; Tama et al, 2000; Atilgan et al, 2001), which were shown to describe conformational changes remarkably well (Tama and Sanejouand, 2001; Delarue and Sanejouand, 2002; Zheng and Doniach, 2003; Mahajan and Sanejouand, 2015). …”

Section: Introductionmentioning

confidence: 99%

Comparative Normal Mode Analysis of the Dynamics of DENV and ZIKV Capsids

Hsieh

Poitevin

Delarue

et al. 2016

Front. Mol. Biosci.

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Key steps in the life cycle of a virus, such as the fusion event as the virus infects a host cell and its maturation process, relate to an intricate interplay between the structure and the dynamics of its constituent proteins, especially those that define its capsid, much akin to an envelope that protects its genomic material. We present a comprehensive, comparative analysis of such interplay for the capsids of two viruses from the flaviviridae family, Dengue (DENV) and Zika (ZIKV). We use for that purpose our own software suite, DD-NMA, which is based on normal mode analysis. We describe the elements of DD-NMA that are relevant to the analysis of large systems, such as virus capsids. In particular, we introduce our implementation of simplified elastic networks and justify their parametrization. Using DD-NMA, we illustrate the importance of packing interactions within the virus capsids on the dynamics of the E proteins of DENV and ZIKV. We identify differences between the computed atomic fluctuations of the E proteins in DENV and ZIKV and relate those differences to changes observed in their high resolution structures. We conclude with a discussion on additional analyses that are needed to fully characterize the dynamics of the two viruses.

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“…Moreover, additional refinements of parameters are presumably needed so as to accurately reproduce long-term structural dynamics. 2,6,7 Another issue is the limited conformational sampling ability of MD due to slow crossing of energy barriers. 8,9 To overcome this problem, enhanced sampling methods have been developed, such as targeted MD, 10 accelerated MD, 11 metadynamics, 12 and replica-exchange MD.…”

Section: Introductionmentioning

confidence: 99%

“…18–23 While these studies showed remarkable success, the increased computational cost with increased system size has been a drawback for applying “classical” NMA in the presence of an atomic force field. 7 ENMs coupled with NMA emerged as alternative, 24 computationally efficient tools for exploring collective dynamics as well as supramolecular machinery. 25 …”

Section: Introductionmentioning

confidence: 99%

ClustENM: ENM-Based Sampling of Essential Conformational Space at Full Atomic Resolution

Kurkcuoglu

Bahar

Doruker

2016

J. Chem. Theory Comput.

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Accurate sampling of conformational space and, in particular, the transitions between functional substates has been a challenge in molecular dynamic (MD) simulations of large biomolecular systems. We developed an Elastic Network Model (ENM)-based computational method, ClustENM, for sampling large conformational changes of biomolecules with various sizes and oligomerization states. ClustENM is an iterative method that combines ENM with energy minimization and clustering steps. It is an unbiased technique, which requires only an initial structure as input, and no information about the target conformation. To test the performance of ClustENM, we applied it to six biomolecular systems: adenylate kinase (AK), calmodulin, p38 MAP kinase, HIV-1 reverse transcriptase (RT), triosephosphate isomerase (TIM), and the 70S ribosomal complex. The generated ensembles of conformers determined at atomic resolution show good agreement with experimental data (979 structures resolved by X-ray and/or NMR) and encompass the subspaces covered in independent MD simulations for TIM, p38, and RT. ClustENM emerges as a computationally efficient tool for characterizing the conformational space of large systems at atomic detail, in addition to generating a representative ensemble of conformers that can be advantageously used in simulating substrate/ligand-binding events.

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On the relationship between low-frequency normal modes and the large-scale conformational changes of proteins

Cited by 69 publications

References 166 publications

Putative model for heat shock protein 70 complexation with receptor of advanced glycation end products through fluorescence proximity assays and normal mode analyses

Putative model for heat shock protein 70 complexation with receptor of advanced glycation end products through fluorescence proximity assays and normal mode analyses

Comparative Normal Mode Analysis of the Dynamics of DENV and ZIKV Capsids

ClustENM: ENM-Based Sampling of Essential Conformational Space at Full Atomic Resolution

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