[English] 日本語
Yorodumi
- PDB-9exz: Efficient and scalable protein design using a relaxed sequence space -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 9exz
TitleEfficient and scalable protein design using a relaxed sequence space
ComponentsDE NOVO PROTEIN P600
KeywordsDE NOVO PROTEIN / P600
Biological speciessynthetic construct (others)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.8 Å
AuthorsFrank, C.J. / Dietz, H.
Funding supportEuropean Union, Germany, 2items
OrganizationGrant numberCountry
European Research Council (ERC)GA101018465European Union
Germanys Excellence StrategyTUM Innovation Network Projekt RISE Germany
CitationJournal: Science / Year: 2024
Title: Scalable protein design using optimization in a relaxed sequence space.
Authors: Christopher Frank / Ali Khoshouei / Lara Fuβ / Dominik Schiwietz / Dominik Putz / Lara Weber / Zhixuan Zhao / Motoyuki Hattori / Shihao Feng / Yosta de Stigter / Sergey Ovchinnikov / Hendrik Dietz /
Abstract: Machine learning (ML)-based design approaches have advanced the field of de novo protein design, with diffusion-based generative methods increasingly dominating protein design pipelines. Here, we ...Machine learning (ML)-based design approaches have advanced the field of de novo protein design, with diffusion-based generative methods increasingly dominating protein design pipelines. Here, we report a "hallucination"-based protein design approach that functions in relaxed sequence space, enabling the efficient design of high-quality protein backbones over multiple scales and with broad scope of application without the need for any form of retraining. We experimentally produced and characterized more than 100 proteins. Three high-resolution crystal structures and two cryo-electron microscopy density maps of designed single-chain proteins comprising up to 1000 amino acids validate the accuracy of the method. Our pipeline can also be used to design synthetic protein-protein interactions, as validated experimentally by a set of protein heterodimers. Relaxed sequence optimization offers attractive performance with respect to designability, scope of applicability for different design problems, and scalability across protein sizes.
History
DepositionApr 9, 2024Deposition site: PDBE / Processing site: PDBE
Revision 1.0Oct 16, 2024Provider: repository / Type: Initial release
Revision 1.1Nov 6, 2024Group: Database references / Category: citation / citation_author
Item: _citation.journal_volume / _citation.page_first ..._citation.journal_volume / _citation.page_first / _citation.page_last / _citation.pdbx_database_id_PubMed / _citation.title

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: DE NOVO PROTEIN P600
B: DE NOVO PROTEIN P600
C: DE NOVO PROTEIN P600


Theoretical massNumber of molelcules
Total (without water)202,4353
Polymers202,4353
Non-polymers00
Water00
1
A: DE NOVO PROTEIN P600


Theoretical massNumber of molelcules
Total (without water)67,4781
Polymers67,4781
Non-polymers00
Water0
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
2
B: DE NOVO PROTEIN P600


Theoretical massNumber of molelcules
Total (without water)67,4781
Polymers67,4781
Non-polymers00
Water0
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
3
C: DE NOVO PROTEIN P600


Theoretical massNumber of molelcules
Total (without water)67,4781
Polymers67,4781
Non-polymers00
Water0
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Unit cell
Length a, b, c (Å)163.249, 67.825, 173.693
Angle α, β, γ (deg.)90.000, 103.200, 90.000
Int Tables number5
Space group name H-MC121
Space group name HallC2y
Symmetry operation#1: x,y,z
#2: -x,y,-z
#3: x+1/2,y+1/2,z
#4: -x+1/2,y+1/2,-z

-
Components

#1: Protein DE NOVO PROTEIN P600


Mass: 67478.477 Da / Num. of mol.: 3
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) synthetic construct (others) / Production host: Escherichia coli (E. coli)
Has protein modificationN

-
Experimental details

-
Experiment

ExperimentMethod: X-RAY DIFFRACTION / Number of used crystals: 1

-
Sample preparation

CrystalDensity Matthews: 2.31 Å3/Da / Density % sol: 46.81 %
Crystal growTemperature: 293 K / Method: vapor diffusion, hanging drop
Details: 20% PEG8000, 0.2 M Calcium acetate hydrate, 0.1 M MES 6.0

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: SSRF / Beamline: BL02U1 / Wavelength: 0.9792 Å
DetectorType: DECTRIS EIGER2 S 9M / Detector: PIXEL / Date: Mar 5, 2024
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.9792 Å / Relative weight: 1
ReflectionResolution: 2.8→50 Å / Num. obs: 45906 / % possible obs: 99.6 % / Redundancy: 3.6 % / Biso Wilson estimate: 55.99 Å2 / CC1/2: 0.998 / Rmerge(I) obs: 0.072 / Rpim(I) all: 0.042 / Net I/σ(I): 15.63
Reflection shellResolution: 2.8→2.9 Å / Redundancy: 3.6 % / Rmerge(I) obs: 0.6917 / Mean I/σ(I) obs: 2.78 / Num. unique obs: 4577 / CC1/2: 0.708 / % possible all: 99.78

-
Processing

Software
NameVersionClassification
PHENIX1.18.1_3865refinement
XDSdata reduction
XDSdata scaling
MOLREPphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT / Resolution: 2.8→42.28 Å / SU ML: 0.3927 / Cross valid method: FREE R-VALUE / σ(F): 1.36 / Phase error: 30.0334
Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2
RfactorNum. reflection% reflection
Rfree0.2785 2278 4.96 %
Rwork0.2368 43628 -
obs0.2389 45906 99.64 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL
Displacement parametersBiso mean: 68.37 Å2
Refinement stepCycle: LAST / Resolution: 2.8→42.28 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms13929 0 0 0 13929
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.012414135
X-RAY DIFFRACTIONf_angle_d1.614719131
X-RAY DIFFRACTIONf_chiral_restr0.08132254
X-RAY DIFFRACTIONf_plane_restr0.00692491
X-RAY DIFFRACTIONf_dihedral_angle_d26.72455416
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
2.8-2.860.36071600.32552700X-RAY DIFFRACTION99.79
2.86-2.930.34981540.30872700X-RAY DIFFRACTION99.69
2.93-30.30321320.29522696X-RAY DIFFRACTION99.54
3-3.080.331250.3052718X-RAY DIFFRACTION99.61
3.08-3.170.3691310.30642737X-RAY DIFFRACTION99.86
3.17-3.270.35391520.30912696X-RAY DIFFRACTION99.51
3.27-3.390.36911200.29112764X-RAY DIFFRACTION99.86
3.39-3.530.34011400.2782691X-RAY DIFFRACTION99.89
3.53-3.690.28661470.26472708X-RAY DIFFRACTION99.96
3.69-3.880.28751400.24692720X-RAY DIFFRACTION99.97
3.88-4.120.29281510.23352718X-RAY DIFFRACTION99.86
4.13-4.440.28841460.20652713X-RAY DIFFRACTION99.06
4.44-4.890.23591410.1992741X-RAY DIFFRACTION99.48
4.89-5.60.25691410.21722743X-RAY DIFFRACTION99.93
5.6-7.040.27681400.24372766X-RAY DIFFRACTION99.73
7.04-42.280.18081580.15352817X-RAY DIFFRACTION98.54

+
About Yorodumi

-
News

-
Feb 9, 2022. New format data for meta-information of EMDB entries

New format data for meta-information of EMDB entries

  • Version 3 of the EMDB header file is now the official format.
  • The previous official version 1.9 will be removed from the archive.

Related info.:EMDB header

External links:wwPDB to switch to version 3 of the EMDB data model

-
Aug 12, 2020. Covid-19 info

Covid-19 info

URL: https://pdbj.org/emnavi/covid19.php

New page: Covid-19 featured information page in EM Navigator.

Related info.:Covid-19 info / Mar 5, 2020. Novel coronavirus structure data

+
Mar 5, 2020. Novel coronavirus structure data

Novel coronavirus structure data

Related info.:Yorodumi Speices / Aug 12, 2020. Covid-19 info

External links:COVID-19 featured content - PDBj / Molecule of the Month (242)：Coronavirus Proteases

+
Jan 31, 2019. EMDB accession codes are about to change! (news from PDBe EMDB page)

EMDB accession codes are about to change! (news from PDBe EMDB page)

  • The allocation of 4 digits for EMDB accession codes will soon come to an end. Whilst these codes will remain in use, new EMDB accession codes will include an additional digit and will expand incrementally as the available range of codes is exhausted. The current 4-digit format prefixed with “EMD-” (i.e. EMD-XXXX) will advance to a 5-digit format (i.e. EMD-XXXXX), and so on. It is currently estimated that the 4-digit codes will be depleted around Spring 2019, at which point the 5-digit format will come into force.
  • The EM Navigator/Yorodumi systems omit the EMD- prefix.

Related info.:Q: What is EMD? / ID/Accession-code notation in Yorodumi/EM Navigator

External links:EMDB Accession Codes are Changing Soon! / Contact to PDBj

+
Jul 12, 2017. Major update of PDB

Major update of PDB

  • wwPDB released updated PDB data conforming to the new PDBx/mmCIF dictionary.
  • This is a major update changing the version number from 4 to 5, and with Remediation, in which all the entries are updated.
  • In this update, many items about electron microscopy experimental information are reorganized (e.g. em_software).
  • Now, EM Navigator and Yorodumi are based on the updated data.

External links:wwPDB Remediation / Enriched Model Files Conforming to OneDep Data Standards Now Available in the PDB FTP Archive

-
Yorodumi

Thousand views of thousand structures

  • Yorodumi is a browser for structure data from EMDB, PDB, SASBDB, etc.
  • This page is also the successor to EM Navigator detail page, and also detail information page/front-end page for Omokage search.
  • The word "yorodu" (or yorozu) is an old Japanese word meaning "ten thousand". "mi" (miru) is to see.

Related info.:EMDB / PDB / SASBDB / Comparison of 3 databanks / Yorodumi Search / Aug 31, 2016. New EM Navigator & Yorodumi / Yorodumi Papers / Jmol/JSmol / Function and homology information / Changes in new EM Navigator and Yorodumi

Read more