X-ray crystallography over the past decade for novel drug discovery -where are we heading next?

Heping Zheng, Katarzyna B. Handing, Matthew D. Zimmerman, Ivan G. Shabalin, Steven C. Almo, Wladek Minor

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Introduction: Macromolecular X-ray crystallography has been the primary methodology for determining the three-dimensional structures of proteins, nucleic acids and viruses. Structural information has paved the way for structure-guided drug discovery and laid the foundations for structural bioinformatics. However, X-ray crystallography still has a few fundamental limitations, some of which may be overcome and complemented using emerging methods and technologies in other areas of structural biology.Areas covered: This review describes how structural knowledge gained from X-ray crystallography has been used to advance other biophysical methods for structure determination (and vice versa). This article also covers current practices for integrating data generated by other biochemical and biophysical methods with those obtained from X-ray crystallography. Finally, the authors articulate their vision about how a combination of structural and biochemical/biophysical methods may improve our understanding of biological processes and interactions.Expert opinion: X-ray crystallography has been, and will continue to serve as, the central source of experimental structural biology data used in the discovery of new drugs. However, other structural biology techniques are useful not only to overcome the major limitation of X-ray crystallography, but also to provide complementary structural data that is useful in drug discovery. The use of recent advancements in biochemical, spectroscopy and bioinformatics methods may revolutionize drug discovery, albeit only when these data are combined and analyzed with effective data management systems. Accurate and complete data management is crucial for developing experimental procedures that are robust and reproducible.

Original languageEnglish (US)
Pages (from-to)975-989
Number of pages15
JournalExpert Opinion on Drug Discovery
Volume10
Issue number9
DOIs
StatePublished - Sep 2 2015

Fingerprint

X Ray Crystallography
Drug Discovery
Computational Biology
Biological Phenomena
Expert Testimony
Information Systems
Nucleic Acids
Spectrum Analysis
Viruses
Technology
Proteins

Keywords

  • data management
  • hybrid methods
  • protein crystallography
  • reproducibility
  • structural data interpretation
  • target-based drug discovery

ASJC Scopus subject areas

  • Drug Discovery

Cite this

X-ray crystallography over the past decade for novel drug discovery -where are we heading next? / Zheng, Heping; Handing, Katarzyna B.; Zimmerman, Matthew D.; Shabalin, Ivan G.; Almo, Steven C.; Minor, Wladek.

In: Expert Opinion on Drug Discovery, Vol. 10, No. 9, 02.09.2015, p. 975-989.

Research output: Contribution to journalArticle

Zheng, Heping ; Handing, Katarzyna B. ; Zimmerman, Matthew D. ; Shabalin, Ivan G. ; Almo, Steven C. ; Minor, Wladek. / X-ray crystallography over the past decade for novel drug discovery -where are we heading next?. In: Expert Opinion on Drug Discovery. 2015 ; Vol. 10, No. 9. pp. 975-989.
@article{c863ba66220c47d68e5e2b0dd666a443,
title = "X-ray crystallography over the past decade for novel drug discovery -where are we heading next?",
abstract = "Introduction: Macromolecular X-ray crystallography has been the primary methodology for determining the three-dimensional structures of proteins, nucleic acids and viruses. Structural information has paved the way for structure-guided drug discovery and laid the foundations for structural bioinformatics. However, X-ray crystallography still has a few fundamental limitations, some of which may be overcome and complemented using emerging methods and technologies in other areas of structural biology.Areas covered: This review describes how structural knowledge gained from X-ray crystallography has been used to advance other biophysical methods for structure determination (and vice versa). This article also covers current practices for integrating data generated by other biochemical and biophysical methods with those obtained from X-ray crystallography. Finally, the authors articulate their vision about how a combination of structural and biochemical/biophysical methods may improve our understanding of biological processes and interactions.Expert opinion: X-ray crystallography has been, and will continue to serve as, the central source of experimental structural biology data used in the discovery of new drugs. However, other structural biology techniques are useful not only to overcome the major limitation of X-ray crystallography, but also to provide complementary structural data that is useful in drug discovery. The use of recent advancements in biochemical, spectroscopy and bioinformatics methods may revolutionize drug discovery, albeit only when these data are combined and analyzed with effective data management systems. Accurate and complete data management is crucial for developing experimental procedures that are robust and reproducible.",
keywords = "data management, hybrid methods, protein crystallography, reproducibility, structural data interpretation, target-based drug discovery",
author = "Heping Zheng and Handing, {Katarzyna B.} and Zimmerman, {Matthew D.} and Shabalin, {Ivan G.} and Almo, {Steven C.} and Wladek Minor",
year = "2015",
month = "9",
day = "2",
doi = "10.1517/17460441.2015.1061991",
language = "English (US)",
volume = "10",
pages = "975--989",
journal = "Expert Opinion on Drug Discovery",
issn = "1746-0441",
publisher = "Informa Healthcare",
number = "9",

}

TY - JOUR

T1 - X-ray crystallography over the past decade for novel drug discovery -where are we heading next?

AU - Zheng, Heping

AU - Handing, Katarzyna B.

AU - Zimmerman, Matthew D.

AU - Shabalin, Ivan G.

AU - Almo, Steven C.

AU - Minor, Wladek

PY - 2015/9/2

Y1 - 2015/9/2

N2 - Introduction: Macromolecular X-ray crystallography has been the primary methodology for determining the three-dimensional structures of proteins, nucleic acids and viruses. Structural information has paved the way for structure-guided drug discovery and laid the foundations for structural bioinformatics. However, X-ray crystallography still has a few fundamental limitations, some of which may be overcome and complemented using emerging methods and technologies in other areas of structural biology.Areas covered: This review describes how structural knowledge gained from X-ray crystallography has been used to advance other biophysical methods for structure determination (and vice versa). This article also covers current practices for integrating data generated by other biochemical and biophysical methods with those obtained from X-ray crystallography. Finally, the authors articulate their vision about how a combination of structural and biochemical/biophysical methods may improve our understanding of biological processes and interactions.Expert opinion: X-ray crystallography has been, and will continue to serve as, the central source of experimental structural biology data used in the discovery of new drugs. However, other structural biology techniques are useful not only to overcome the major limitation of X-ray crystallography, but also to provide complementary structural data that is useful in drug discovery. The use of recent advancements in biochemical, spectroscopy and bioinformatics methods may revolutionize drug discovery, albeit only when these data are combined and analyzed with effective data management systems. Accurate and complete data management is crucial for developing experimental procedures that are robust and reproducible.

AB - Introduction: Macromolecular X-ray crystallography has been the primary methodology for determining the three-dimensional structures of proteins, nucleic acids and viruses. Structural information has paved the way for structure-guided drug discovery and laid the foundations for structural bioinformatics. However, X-ray crystallography still has a few fundamental limitations, some of which may be overcome and complemented using emerging methods and technologies in other areas of structural biology.Areas covered: This review describes how structural knowledge gained from X-ray crystallography has been used to advance other biophysical methods for structure determination (and vice versa). This article also covers current practices for integrating data generated by other biochemical and biophysical methods with those obtained from X-ray crystallography. Finally, the authors articulate their vision about how a combination of structural and biochemical/biophysical methods may improve our understanding of biological processes and interactions.Expert opinion: X-ray crystallography has been, and will continue to serve as, the central source of experimental structural biology data used in the discovery of new drugs. However, other structural biology techniques are useful not only to overcome the major limitation of X-ray crystallography, but also to provide complementary structural data that is useful in drug discovery. The use of recent advancements in biochemical, spectroscopy and bioinformatics methods may revolutionize drug discovery, albeit only when these data are combined and analyzed with effective data management systems. Accurate and complete data management is crucial for developing experimental procedures that are robust and reproducible.

KW - data management

KW - hybrid methods

KW - protein crystallography

KW - reproducibility

KW - structural data interpretation

KW - target-based drug discovery

UR - http://www.scopus.com/inward/record.url?scp=84938937218&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84938937218&partnerID=8YFLogxK

U2 - 10.1517/17460441.2015.1061991

DO - 10.1517/17460441.2015.1061991

M3 - Article

VL - 10

SP - 975

EP - 989

JO - Expert Opinion on Drug Discovery

JF - Expert Opinion on Drug Discovery

SN - 1746-0441

IS - 9

ER -