The Many Roles of Computation in Drug Discovery

@article{Jorgensen2004TheMR,
  title={The Many Roles of Computation in Drug Discovery},
  author={William L. Jorgensen},
  journal={Science},
  year={2004},
  volume={303},
  pages={1813 - 1818}
}
An overview is given on the diverse uses of computational chemistry in drug discovery. Particular emphasis is placed on virtual screening, de novo design, evaluation of drug-likeness, and advanced methods for determining protein-ligand binding. 

Topics from this paper

Comparative Modeling of Drug Target Proteins
TLDR
In this perspective, the comparative protein structure modeling technique and the accuracy of the corresponding models are described and the significant role that comparative prediction plays in drug discovery is discussed. Expand
Comparative Modeling of Drug Target Proteins☆
Abstract In this perspective, we begin by describing the comparative protein structure modeling technique and the accuracy of the corresponding models. WeExpand
Computational Methods in Medicinal Chemistry : Mechanistic Investigations and Virtual Screening Development
Computational methods have become an integral part of drug development and can help bring new and better drugs to the market faster. The process of predicting the biological activity of large compoExpand
Multivariate design of molecular docking experiments : An investigation of protein-ligand interactions
To be able to make informed descicions regarding the research of new drug molecules (ligands), it is crucial to have access to information regarding the chemical interaction between the drug and itExpand
Frontiers in Computational Chemistry for Drug Discovery
TLDR
Computational methods pervade almost all aspects of drug discovery and have a fundamental role in drug discovery. Expand
Modeling the Interaction Space of Biological Macromolecules: A Proteochemometric Approach : Applications for Drug Discovery and Development
TLDR
The ability to model and predict interactions of any biological molecule to recognize and predict those of other molecules is key to understanding molecular recognition processes and their applications in medicine. Expand
Current and emerging opportunities for molecular simulations in structure-based drug design
  • J. Michel
  • Chemistry, Medicine
  • Physical chemistry chemical physics : PCCP
  • 2014
Opportunities are reviewed for state-of-the-art molecular simulations to progress the understanding of the molecular driving forces of protein–ligand association, assist interpretation of biophysicalExpand
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
Virtual screening and new drug discovery
TLDR
This review will introduce recent advances in virtual screening and its function in new drug discovery, and discuss the research situation of virtual screening in this country. Expand
Computational Methods in Multitarget Drug Discovery
Abstract Today, computational methods are commonly adopted in practically every stage of the drug discovery process, performing an efficient screening of virtual libraries for hit identification,Expand
...
1
2
3
4
5
...

References

SHOWING 1-10 OF 132 REFERENCES
A review of protein-small molecule docking methods
TLDR
An overview of current docking techniques is presented with a description of applications including single docking experiments and the virtual screening of databases. Expand
Prediction of 'drug-likeness'.
TLDR
A number of computational techniques for identifying drug-like molecules are reviewed and challenges facing the field are examined. Expand
A new method for predicting binding affinity in computer-aided drug design.
A new semi-empirical method for calculating free energies of binding from molecular dynamics (MD) simulations is presented. It is based on standard thermodynamic cycles and on a linear approximationExpand
Computational approaches to molecular recognition.
TLDR
Recent advances in the computation of free energies have facilitated the understanding of host-guest and protein-ligand recognition and more approximate techniques have been developed that allow faster treatment of diverse systems. Expand
Lead discovery using molecular docking.
TLDR
As the structures of more and more proteins and nucleic acids become available, molecular docking is increasingly considered for lead discovery and the 'drug-likeness' and specificity of docking hits is also being examined. Expand
Virtual screening : an overview
TLDR
This review presents the current state of the art in virtual screening and discusses approaches that will allow the evaluation of larger numbers of compounds. Expand
Prediction of drug solubility from structure.
TLDR
Viable methods now exist for predictions with less than 1 log unit uncertainty, which is adequate for prescreening synthetic candidates or design of combinatorial libraries, which would require an experimental database of highly accurate solubilities for a large, diverse collection of drug-like molecules. Expand
Molecular docking and high-throughput screening for novel inhibitors of protein tyrosine phosphatase-1B.
TLDR
The diversity of both hit lists and their dissimilarity from each other suggest that docking and HTS may be complementary techniques for lead discovery. Expand
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
Development and validation of a genetic algorithm for flexible docking.
TLDR
GOLD (Genetic Optimisation for Ligand Docking) is an automated ligand docking program that uses a genetic algorithm to explore the full range of ligand conformational flexibility with partial flexibility of the protein, and satisfies the fundamental requirement that the ligand must displace loosely bound water on binding. Expand
...
1
2
3
4
5
...