Fast procedure for reconstruction of full‐atom protein models from reduced representations

Rotkiewicz, Piotr; Skolnick, Jeffrey

doi:10.1002/jcc.20906

Cited by 361 publications

(394 citation statements)

References 17 publications

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“…The first PCA components describe the large-scale collective motions of a structure, which are of functional relevance and are also similar to the normal modes from ENMs. We used Brownian dynamics (BD) 36,37 to populate ensembles along the first PCA component and obtained the results presented in Fig. 3, which highlights the regions in which long-range correlations are observed in 12 selected proteins.…”

Section: Resultsmentioning

confidence: 99%

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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: Resultsmentioning

confidence: 99%

“…The backbone coordinates of the resulting 1,000 trajectory frames were then reconstructed using PULCHRA, which optimizes the hydrogen bonding geometry for the backbone atoms 37 . The circular correlation coefficients were then calculated for all the motifs in these structures.…”

Section: Methodsmentioning

confidence: 99%

Correlated motions are a fundamental property of β-sheets

et al. 2014

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“…There is no direct information on the side chain coordinates, their effects are accounted for implicitly by the interactions in (3). Once we have found a minimal energy Cα structure, we can reconstruct an Ansatz for the all atom structure using side chain libraries; here we use Pulchra [42]. We can then employ MD to refine the ensuing side chain structure if need be [6].…”

Section: Side Chains In Mean Field Approachmentioning

confidence: 99%

Multistage modeling of protein dynamics with monomeric Myc oncoprotein as an example

Liu

Dai

et al. 2017

Phys. Rev. E

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We propose to combine a mean field approach with all atom molecular dynamics (MD), into a multistage algorithm that can model protein folding and dynamics over very long time periods yet with atomic level precision. As an example we investigate an isolated monomeric Myc oncoprotein that has been implicated in carcinomas including those in colon, breast and lungs. Under physiological conditions a monomeric Myc is presumed to be an example of intrinsically disordered proteins, that pose a serious challenge to existing modelling techniques. We argue that a room temperature monomeric Myc is in a dynamical state, it oscillates between different conformations that we identify. For this we adopt the Cα backbone of Myc in a crystallographic heteromer as an initial Ansatz for the monomeric structure. We construct a multisoliton of the pertinent Landau free energy, to describe the Cα profile with ultra high precision. We use Glauber dynamics to resolve how the multisoliton responds to repeated increases and decreases in ambient temperature. We confirm that the initial structure is unstable in isolation. We reveal a highly degenerate ground state landscape, an attractive set towards which Glauber dynamics converges in the limit of vanishing ambient temperature. We analyse the thermal stability of this Glauber attractor using room temperature molecular dynamics. We identify and scrutinise a particularly stable subset in which the two helical segments of the original multisoliton align in parallel, next to each other. During the MD time evolution of a representative structure from this subset, we observe intermittent quasiparticle oscillations along the C-terminal α-helix, some of which resemble a translating Davydov's Amide-I soliton. We propose that the presence of oscillatory motion is in line with the expected intrinsically disordered character of Myc.

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“…22 The Ca trace was then refined to produce a full atomic structure. First, the backbone atoms were added using the program pulchra 24 followed by the addition of the side chain rotamers by SCRWL. 25 The full atomic structure thus obtained was further refined using Fragment Guided Molecular Dynamics (FG-MD) 26 to generate an energetically reasonable structure.…”

Section: Fitting Of Cryoem Density Map Into Negative Stain Density Mapmentioning

confidence: 99%

Three dimensional structure of the anthrax toxin translocon–lethal factor complex by cryo‐electron microscopy

et al. 2013

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We have visualized by cryo-electron microscopy (cryo-EM) the complex of the anthrax protective antigen (PA) translocon and the N-terminal domain of anthrax lethal factor (LF N ) inserted into a nanodisc model lipid bilayer. We have determined the structure of this complex at a nominal resolution of 16 Å by single-particle analysis and three-dimensional reconstruction. Consistent with our previous analysis of negatively stained unliganded PA, the translocon comprises a globular structure (cap) separated from the nanodisc bilayer by a narrow stalk that terminates in a transmembrane channel (incompletely distinguished in this reconstruction). The globular cap is larger than the unliganded PA pore, probably due to distortions introduced in the previous negatively stained structures. The cap exhibits larger, more distinct radial protrusions, previously identified with PA domain three, fitted by elements of the NMFF PA prepore crystal structure. The presence of LF N , though not distinguished due to the seven-fold averaging used in the reconstruction, contributes to the distinct protrusions on the cap rim volume distal to the membrane. Furthermore, the lumen of the cap region is less resolved than the unliganded negatively stained PA, due to the low contrast obtained in our images of this specimen. Presence of the LF N extended helix and N terminal unstructured regions may also contribute to this additional internal density within the interior of the cap. Initial NMFF fitting of the cryoEM-defined PA pore cap region positions the Phe clamp region of the PA pore translocon directly above an internal vestibule, consistent with its role in toxin translocation.

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Fast procedure for reconstruction of full‐atom protein models from reduced representations

Cited by 361 publications

References 17 publications

Correlated motions are a fundamental property of β-sheets

Correlated motions are a fundamental property of β-sheets

Multistage modeling of protein dynamics with monomeric Myc oncoprotein as an example

Three dimensional structure of the anthrax toxin translocon–lethal factor complex by cryo‐electron microscopy

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