Fragment library design: efficiently hunting drugs in chemical space

2010 ◽  
Vol 7 (3) ◽  
pp. e173-e180 ◽  
Author(s):  
Susan M. Boyd ◽  
Gerdien E. de Kloe
Keyword(s):  
Chemical Space ◽  
Library Design ◽  
Fragment Library

scholarly journals How Size Matters: Designing Diverse Fragment Libraries for Novel Drug Discovery

Proceedings ◽  
2019 ◽  
Vol 22 (1) ◽  
pp. 107
Author(s):  
Yun Shi ◽  
Mark von Itzstein
Keyword(s):  
Drug Discovery ◽  
Chemical Space ◽  
Structural Diversity ◽  
Optimal Size ◽  
Zinc Database ◽  
Fragment Library ◽  
Size Diversity ◽  
Efficient Exploration ◽  
Novel Drug ◽  
Fragment Libraries

Fragment-based drug discovery (FBDD) has become a major strategy to derive novel lead candidates for both new and established therapeutic targets, as it promises efficient exploration of chemical space by employing fragment-sized (MW 300) compounds. One of the first challenges in implementing a FBDD approach is the design of a fragment library, and more specifically, the choice of its size and individual members. In order to construct a library that maximises the chances of discovering novel chemical matter, a large number of fragments with sufficient structural diversity are often sought. However, the exact diversity of a certain collection of fragments remains elusive, which hinders direct comparisons among different selections of fragments. Building upon structural fingerprints that are commonly utilised in cheminformatics, we herein introduced quantitative measures for the structural diversity of fragment libraries. Structures of commercially available fragments were retrieved from the ZINC database and filtered by physicochemical properties, after which they were subject to selections with library sizes ranging from 100 to 100,000 compounds. The selected libraries were evaluated and compared quantitatively, resulting in interesting size-diversity relationships. Our results suggested the existence of an optimal size for structural diversity and demonstrated that such quantitative measures can guide the design of diverse fragment libraries under various circumstances

Design of a Fragment Library that maximally represents available chemical space

2011 ◽  
Vol 25 (7) ◽  
pp. 611-620 ◽  
Author(s):  
M. N. Schulz ◽  
J. Landström ◽  
K. Bright ◽  
R. E. Hubbard
Keyword(s):  
Chemical Space ◽  
Fragment Library

Monash Fragment Platform

Impact ◽  
2018 ◽  
Vol 2018 (3) ◽  
pp. 32-34
Author(s):  
Martin Scanlon
Keyword(s):  
Surface Plasmon Resonance ◽  
Nmr Spectroscopy ◽  
Structural Biology ◽  
State Of The Art ◽  
Chemical Space ◽  
Pharmaceutical Sciences ◽  
High Quality ◽  
Fragment Library ◽  
Pharmaceutical Institute ◽  
Fragment Based Drug Discovery

The Monash Fragment Platform (MFP) provides academic and commercial researchers with access to fragment-based drug discovery (FBDD) technologies for their therapeutic targets. The facilities are located at the Monash Institute for Pharmaceutical Sciences (MIPS) in Parkville, Australia's largest and most successful pharmaceutical institute. FBDD screening uses our high-quality, in-house fragment library designed to maximise chemical space coverage and enable rapid hit optimisation. Screening cascades are tailored for each target and can be performed using a variety of techniques including NMR spectroscopy and our state-of-the-art surface plasmon resonance (SPR) facility. Structural biology and medicinal chemistry expertise utilising our standardized REFIL strategy enables the rapid elaboration of fragments into leads without the requirement for a large chemistry program.

scholarly journals MoleGear: A Java-Based Platform for Evolutionary De Novo Molecular Design

Molecules ◽  
2019 ◽  
Vol 24 (7) ◽  
pp. 1444 ◽  
Author(s):  
Chu ◽  
He
Keyword(s):  
Large Scale ◽  
De Novo ◽  
Molecular Design ◽  
Chemical Space ◽  
Binding Free Energy ◽  
Fitness Function ◽  
Chemistry Development ◽  
Fragment Library ◽  
Immunodeficiency Virus ◽  
De Novo Molecular Design

A Java-based platform, MoleGear, is developed for de novo molecular design based on the chemistry development kit (CDK) and other Java packages. MoleGear uses evolutionary algorithm (EA) to explore chemical space, and a suite of fragment-based operators of growing, crossover, and mutation for assembling novel molecules that can be scored by prediction of binding free energy or a weighted-sum multi-objective fitness function. The EA can be conducted in parallel over multiple nodes to support large-scale molecular optimizations. Some complementary utilities such as fragment library design, chemical space analysis, and graphical user interface are also integrated into MoleGear. The candidate molecules as inhibitors for the human immunodeficiency virus 1 (HIV-1) protease were designed by MoleGear, which validates the potential capability for de novo molecular design.

scholarly journals How Size Matters: Diversity for Fragment Library Design

Molecules ◽  
2019 ◽  
Vol 24 (15) ◽  
pp. 2838 ◽  
Author(s):  
Yun Shi ◽  
Mark von Itzstein
Keyword(s):  
Chemical Space ◽  
Structural Diversity ◽  
Optimal Size ◽  
Library Size ◽  
Quantitative Metrics ◽  
Zinc Database ◽  
Fragment Library ◽  
Size Diversity ◽  
Efficient Exploration ◽  
Fragment Libraries

Fragment-based drug discovery (FBDD) has become a major strategy to derive novel lead candidates for various therapeutic targets, as it promises efficient exploration of chemical space by employing fragment-sized (MW < 300) compounds. One of the first challenges in implementing a FBDD approach is the design of a fragment library, and more specifically, the choice of its size and individual members. A diverse set of fragments is required to maximize the chances of discovering novel hit compounds. However, the exact diversity of a certain collection of fragments remains underdefined, which hinders direct comparisons among different selections of fragments. Based on structural fingerprints, we herein introduced quantitative metrics for the structural diversity of fragment libraries. Structures of commercially available fragments were retrieved from the ZINC database, from which libraries with sizes ranging from 100 to 100,000 compounds were selected. The selected libraries were evaluated and compared quantitatively, resulting in interesting size-diversity relationships. Our results demonstrated that while library size does matter for its diversity, there exists an optimal size for structural diversity. It is also suggested that such quantitative measures can guide the design of diverse fragment libraries under different circumstances.

scholarly journals Fragment library design, synthesis and expansion: nurturing a synthesis and training platform

2017 ◽  
Vol 22 (1) ◽  
pp. 43-56 ◽  
Author(s):  
Peter C. Ray ◽  
Michael Kiczun ◽  
Margaret Huggett ◽  
Andrew Lim ◽  
Federica Prati ◽  
...  
Keyword(s):  
Library Design ◽  
Design Synthesis ◽  
Fragment Library ◽  
And Training

Fragment library design considerations

2012 ◽  
Vol 2 (6) ◽  
pp. 868-885 ◽  
Author(s):  
Susan M. Boyd ◽  
Andrew P. Turnbull ◽  
Björn Walse
Keyword(s):  
Library Design ◽  
Design Considerations ◽  
Fragment Library
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