New tools and functions in data‐out activities at Protein Data Bank Japan (PDBj)

Kinjo, Akira R.; Bekker, Gert‐Jan; Wako, Hiroshi; Endo, Shigeru; Tsuchiya, Yuko; Sato, Hiromu; Nishi, Hafumi; Kinoshita, Kengo; Suzuki, Hirofumi; Kawabata, Takeshi; Yokochi, Masashi; Iwata, Takeshi; Kobayashi, Naohiro; Fujiwara, Toshimichi; Kurisu, Genji; Nakamura, Haruki

doi:10.1002/pro.3273

Cited by 95 publications

(66 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The Hsp90 structure in complex with the ligand BSM with PDB ID 2BSM [ 34 ] (resolution 2.05 Å) was obtained from Protein Data Bank Japan. [ 35–37 ] The ligand was altered so that it matches that of Compound 3, or VER49008, studied by Schmidtke et al, [ 33 ] to which we from here on refer to as CPD3. The N‐terminal side of Hsp90 was capped with an ACE (acetyl) residue, while the C‐terminal Lys224 of the X‐ray structure, which is almost completely unobserved, was replaced with an NME (N‐methylamide) cap.…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Exhaustive search of the configurational space of heat‐shock protein 90 with its inhibitor by multicanonical molecular dynamics based dynamic docking

et al. 2020

View full text Add to dashboard Cite

Multicanonical molecular dynamics based dynamic docking was used to exhaustively search the configurational space of an inhibitor binding to the N-terminal domain of heat-shock protein 90 (Hsp90). The obtained structures at 300 K cover a wide structural ensemble, with the top two clusters ranked by their free energy coinciding with the native binding site. The representative structure of the most stable cluster reproduced the experimental binding configuration, but an interesting conformational change in Hsp90 could be observed. The combined effects of solvation and ligand binding shift the equilibrium from a preferred loop-in conformation in the unbound state to an α-helical one in the bound state for the flexible lid region of Hsp90. Thus, our dynamic docking method is effective at predicting the native binding site while exhaustively sampling a wide configurational space, modulating the protein structure upon binding. K E Y W O R D S dynamic docking, enhanced conformational sampling, free energy landscape, heat-shock protein 90, multicanonical Molecular Dynamics

show abstract

Section: Methodsmentioning

confidence: 99%

“…The image was drawn using Molmil. [ 35,36,38 ] Abbreviations: Hsp90, heat‐shock protein 90 [Color figure can be viewed at wileyonlinelibrary.com]…”

Section: Methodsmentioning

confidence: 99%

Exhaustive search of the configurational space of heat‐shock protein 90 with its inhibitor by multicanonical molecular dynamics based dynamic docking

et al. 2020

View full text Add to dashboard Cite

show abstract

“…To provide a comprehensive analysis of structure quality over time, we examined all X-ray structures available in the PDB that included 141 154 deposits between 1972 and 2019. The data were downloaded by performing an SQL query on PDBj [36,37] as of December 10, 2019.…”

Section: Data Collection and Cleaningmentioning

confidence: 99%

On the evolution of the quality of macromolecular models in the PDB

et al. 2020

View full text Add to dashboard Cite

Crystallographic models of biological macromolecules have been ranked using the quality criteria associated with them in the Protein Data Bank (PDB). The outcomes of this quality analysis have been correlated with time and with the journals that published papers based on those models. The results show that the overall quality of PDB structures has substantially improved over the last ten years, but this period of progress was preceded by several years of stagnation or even depression. Moreover, the study shows that the historically observed negative correlation between journal impact and the quality of structural models presented therein seems to disappear as time progresses.

show abstract

“…In the normal mode calculations, molecules bound to proteins (HETATM in PDB data) are excluded, except for thiamine thiazolone diphosphate in BFD. Active sites are also indicated if they are available from PDBj (residues 15, 29, 95, 96, 168, and 284 in ErA; and 28, 70, and 281 in BFD) [40].…”

Section: Interface Residues Between Subunitsmentioning

confidence: 99%

Dynamic properties of oligomers that characterize low-frequency normal modes

Wako

Endo

2019

BIOPHYSICS

Self Cite

View full text Add to dashboard Cite

Dynamics of oligomeric proteins (one trimer, two tetramers, and one hexamer) were studied by elastic network model-based normal mode analysis to characterize their large-scale concerted motions. First, the oligomer motions were simplified by considering rigid-body motions of individual subunits. The subunit motions were resolved into three components in a cylindrical coordinate system: radial, tangential, and axial ones. Single component is dominant in certain normal modes. However, more than one component is mixed in others. The subunits move symmetrically in certain normal modes and as a standing wave with several wave nodes in others. Secondly, special attention was paid to atoms on inter-subunit interfaces. Their displacement vectors were decomposed into intrasubunit deformative (internal) and rigid-body (external) motions in individual subunits. The fact that most of the cosines of the internal and external motion vectors were negative for the atoms on the inter-subunit interfaces, indicated their opposing movements. Finally, a structural network of residues defined for each normal mode was investigated; the network was constructed by connecting two residues in contact and moving coherently. The centrality measure "betweenness" of each residue was calculated for the networks. Several residues with significantly high betweenness were observed on the inter-subunit interfaces. The results indicate that these residues are responsible for oligomer dynamics. It was also observed that amino acid residues with significantly high betweenness were more conservative. This supports that the betweenness is an effective characteristic for identifying an important residue in protein dynamics.Key words: betweenness, degeneracy of normal modes, conservation of amino acid residues, protein structure network, cylindrical coordinate system Most proteins function in an oligomeric form [1]. An advantage of oligomers over monomers is that the oligomeric form permits proteins to initiate allostery and cooperativity in achieving their function. Studies on the dynamics of oligomers can provide key information that reveals the mechanism of the allostery and cooperativity. Molecular dynamics (MD) simulation and normal mode analysis (NMA) can be effective theoretical methods to address this problem [2-9]. Although they can generate a large amount of data regarding protein motions at the atomic level and the motions Dynamics of oligomeric proteins were studied by elastic network model-based normal mode analysis to characterize their large-scale concerted motions. (1) The rigid-body motions of individual subunits were characterized by the radial, tangential, and axial components in a cylindrical coordinate system. (2) The motions of atoms on the intersubunit interfaces were characterized by the opposing motions of intra-subunit deformation and rigid-body motion of the subunit. (3) A dynamic protein structure network was defined in each mode, and the centrality measure, betweenness, was calculated for each residue. The results indicate tha...

show abstract

New tools and functions in data‐out activities at Protein Data Bank Japan (PDBj)

Cited by 95 publications

References 30 publications

Exhaustive search of the configurational space of heat‐shock protein 90 with its inhibitor by multicanonical molecular dynamics based dynamic docking

Exhaustive search of the configurational space of heat‐shock protein 90 with its inhibitor by multicanonical molecular dynamics based dynamic docking

On the evolution of the quality of macromolecular models in the PDB

Dynamic properties of oligomers that characterize low-frequency normal modes

Contact Info

Product

Resources

About