Computer-based de novo design of drug-like molecules

@article{Schneider2005ComputerbasedDN,
  title={Computer-based de novo design of drug-like molecules},
  author={G. Schneider and U. Fechner},
  journal={Nature Reviews Drug Discovery},
  year={2005},
  volume={4},
  pages={649-663}
}
Ever since the first automated de novo design techniques were conceived only 15 years ago, the computer-based design of hit and lead structure candidates has emerged as a complementary approach to high-throughput screening. Although many challenges remain, de novo design supports drug discovery projects by generating novel pharmaceutically active agents with desired properties in a cost- and time-efficient manner. In this review, we outline the various design concepts and highlight current… Expand

Figures, Tables, and Topics from this paper

De novo drug design.
TLDR
State-of-the-art software for de novo drug design with a special emphasis on fragment-based techniques that generate druglike, synthetically accessible compounds are reviewed, and the importance of scoring functions that can be used to predict compound reactivity and potency is highlighted. Expand
De novo design - hop(p)ing against hope.
  • G. Schneider
  • Computer Science, Medicine
  • Drug discovery today. Technologies
  • 2013
TLDR
Current trends in computational de novo design provide a fresh approach to 'scaffold-hopping' in drug discovery, and advanced mathematical models of structure-activity landscapes and multi-objective design techniques have created new opportunities for hit and lead finding. Expand
De Novo Fragment Design for Drug Discovery and Chemical Biology.
TLDR
The study validates computational de novo design as a prime method for generating chemical probes and starting points for drug discovery and identifies additional macromolecular targets of the computationally designed compound and the structurally related marketed drug azosemide. Expand
4.13 – De Novo Design
The value of de novo drug design is assessed within both structure-based and ligand-based formats. Common algorithmic pathways are highlighted for different de novo approaches. Likewise, problemsExpand
De novo computer-aided design of novel antiviral agents.
Computer-aided drug design techniques have become an integral part of the drug discovery process. In particular, de novo methodologies can be useful to identify putative ligands for a specific targetExpand
De Novo Design of Ligands Using Computational Methods.
TLDR
This chapter outlines the basic de novo design concepts based on computational methods with an example of a drug development process. Expand
Enabling future drug discovery by de novo design
TLDR
An overview of the various methodologies for virtual compound construction, evaluation, and optimization in machina, and how they can support medicinal chemistry projects in the early phase of drug discovery is given. Expand
Fragment-based approaches and computer-aided drug discovery.
  • D. Rognan
  • Chemistry, Medicine
  • Topics in current chemistry
  • 2012
TLDR
The present review illustrates the importance of molecular fragments in many aspects of rational ligand design, and discusses how thinking in "fragment space" has boosted computational biology and chemistry. Expand
De Novo Design at the Edge of Chaos.
TLDR
The current perspective on the concept of automated molecule generation is presented by highlighting chemocentric methods that may capture druglike chemical space, consider ligand promiscuity for hit and lead finding, and provide fresh ideas for the rational design of customized screening of compound libraries. Expand
Computer-aided drug design: lead discovery and optimization.
TLDR
The generation of initial lead compounds and the subsequent optimization aimed at improving potency and pharmacological properties are the core activities among all. Expand
...
1
2
3
4
5
...

References

SHOWING 1-10 OF 123 REFERENCES
Trends in virtual combinatorial library design.
  • G. Schneider
  • Chemistry, Medicine
  • Current medicinal chemistry
  • 2002
TLDR
Three major trends have been identified: i) the design of small target-focused compound libraries yielding activity-enriched sets of molecules; ii) advanced prediction methods for "drug-like" molecular properties complement activity predictions in the library design process, forming a multi-dimensional objective function. Expand
BUILDER v.2: Improving the chemistry of a de novo design strategy
  • D. Roe, I. Kuntz
  • Computer Science, Medicine
  • J. Comput. Aided Mol. Des.
  • 1995
TLDR
The bridging algorithm has been further developed and applied to rebuild known bridges in methotrexate and HIV protease to improve the chemical sense and diversity of the bridges, as well as the robustness of the technique. Expand
Development and testing of a de novo drug-design algorithm
TLDR
An implementation of a de novo drug-design algorithm that starts with a molecule placed in the binding site of a protein and then modifies it using a sequential growth approach to create, characterize and evaluate putative ligands. Expand
De novo design of enzyme inhibitors by Monte Carlo ligand generation.
TLDR
A new computational method for the in situ generation of small molecules within the binding site of a protein is described, which resulted in a compound selected for preclinical studies as an antiviral agent against AIDS. Expand
Recent development and application of virtual screening in drug discovery: an overview.
TLDR
Emphasis is placed on aspects of recent development of docking- based virtual screening, scoring functions in molecular docking and ADME/Tox-based virtual screening in the past three years. Expand
De novo design of molecular architectures by evolutionary assembly of drug-derived building blocks
TLDR
The efficiency of the design algorithm was demonstrated for the de novo construction of potential thrombin inhibitors mimicking peptide and non-peptide template structures and the concept of varying library `diversity' during a design process was consequently implemented by using adaptive variant distributions. Expand
Automatic creation of drug candidate structures based on receptor structure. Starting point for artificial lead generation
Abstract We have developed a new method for automatic generation of drug candidate structures based on a known receptor structure. In our method, various structures which fit well to the receptorExpand
SPROUT: Recent developments in the de novo design of molecules
SPROUT is a computer program for constrained structure generation. It is designed to generate molecules for a range of applications in molecular recognition. The program uses a number ofExpand
PRO_LIGAND: An approach to de novo molecular design. 1. Application to the design of organic molecules
TLDR
Pro_LIGAND's efficacy in aiding rational drug design is demonstrated by its ability to design mimics of methotrexate and potential inhibitors for dihydrofolate reductase and HIV-1 protease. Expand
Using NMR for ligand discovery and optimization.
Several recent technology-driven advances in the area of NMR have rekindled an interest in the application of the technology to problems in drug discovery and development. A unique aspect of NMR isExpand
...
1
2
3
4
5
...