Informatics and modeling challenges in fragment-based drug discovery

Roderick E. Hubbard; Ijen Chen; Ben Davis

Informatics and modeling challenges in fragment-based drug discovery

Roderick E. Hubbard, Ijen Chen, Ben Davis

Chemistry

Research output: Contribution to journal › Literature review › peer-review

Abstract

This review summarizes recent developments in fragment-based drug-discovery methods with an emphasis on informatics and modeling requirements. Fragment-based methods have become established as a powerful approach in structure-based lead discovery. A number of successful projects have been announced recently, where fragments have had a central role in hit generation and lead optimization, leading to candidates being considered for clinical trials. Despite these successes, there are still many opportunities for new development, such as improving the structural diversity of fragment libraries, strategies for fragment evolution, and methods for predicting fragment binding modes.

Original language	English
Pages (from-to)	289-297
Number of pages	9
Journal	CURRENT OPINION IN DRUG DISCOVERY
Volume	10
Issue number	3
Publication status	Published - May 2007

Keywords

fragment-based discovery
fragments
NMR
SAR by NMR
structure-based drug discovery
MAP KINASE INHIBITORS
LEAD DISCOVERY
PROTEIN TARGETS
SMALL MOLECULES
LIGAND-BINDING
DESIGN
DOCKING
CRYSTALLOGRAPHY
IDENTIFICATION

Cite this

@article{e499837ac44046c38758891eb73fb318,

title = "Informatics and modeling challenges in fragment-based drug discovery",

abstract = "This review summarizes recent developments in fragment-based drug-discovery methods with an emphasis on informatics and modeling requirements. Fragment-based methods have become established as a powerful approach in structure-based lead discovery. A number of successful projects have been announced recently, where fragments have had a central role in hit generation and lead optimization, leading to candidates being considered for clinical trials. Despite these successes, there are still many opportunities for new development, such as improving the structural diversity of fragment libraries, strategies for fragment evolution, and methods for predicting fragment binding modes.",

keywords = "fragment-based discovery, fragments, NMR, SAR by NMR, structure-based drug discovery, MAP KINASE INHIBITORS, LEAD DISCOVERY, PROTEIN TARGETS, SMALL MOLECULES, LIGAND-BINDING, DESIGN, DOCKING, CRYSTALLOGRAPHY, IDENTIFICATION",

author = "Hubbard, {Roderick E.} and Ijen Chen and Ben Davis",

year = "2007",

month = may,

language = "English",

volume = "10",

pages = "289--297",

journal = "CURRENT OPINION IN DRUG DISCOVERY",

issn = "1367-6733",

publisher = "Current Drugs Ltd.",

number = "3",

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TY - JOUR

T1 - Informatics and modeling challenges in fragment-based drug discovery

AU - Hubbard, Roderick E.

AU - Chen, Ijen

AU - Davis, Ben

PY - 2007/5

Y1 - 2007/5

N2 - This review summarizes recent developments in fragment-based drug-discovery methods with an emphasis on informatics and modeling requirements. Fragment-based methods have become established as a powerful approach in structure-based lead discovery. A number of successful projects have been announced recently, where fragments have had a central role in hit generation and lead optimization, leading to candidates being considered for clinical trials. Despite these successes, there are still many opportunities for new development, such as improving the structural diversity of fragment libraries, strategies for fragment evolution, and methods for predicting fragment binding modes.

AB - This review summarizes recent developments in fragment-based drug-discovery methods with an emphasis on informatics and modeling requirements. Fragment-based methods have become established as a powerful approach in structure-based lead discovery. A number of successful projects have been announced recently, where fragments have had a central role in hit generation and lead optimization, leading to candidates being considered for clinical trials. Despite these successes, there are still many opportunities for new development, such as improving the structural diversity of fragment libraries, strategies for fragment evolution, and methods for predicting fragment binding modes.

KW - fragment-based discovery

KW - fragments

KW - NMR

KW - SAR by NMR

KW - structure-based drug discovery

KW - MAP KINASE INHIBITORS

KW - LEAD DISCOVERY

KW - PROTEIN TARGETS

KW - SMALL MOLECULES

KW - LIGAND-BINDING

KW - DESIGN

KW - DOCKING

KW - CRYSTALLOGRAPHY

KW - IDENTIFICATION

M3 - Literature review

SN - 1367-6733

VL - 10

SP - 289

EP - 297

JO - CURRENT OPINION IN DRUG DISCOVERY

JF - CURRENT OPINION IN DRUG DISCOVERY

IS - 3

ER -