Ligand Design Methods

There are six major classes of ligand design methods  

Like all classification schemes, this one is somewhat arbitrary. Issues to keep in mind when trying to classify these methods include  

Alternate uses Some methods can be adapted for alternatives uses. For example, DOCK, which is clearly a whole molecule approach, also may be viewed as a fragment placement method because it can be used with a library of small fragments to determine optimal locations for those fragments. 

Combination approaches Many of the methods may be combined in various ways to produce what are in effect raultistep approaches. 

Other Factors to Consider When Evaluating a Ligand Design Method 

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M A 1997. Recent Advances in Ligand Design Methods. In Lipkowitz K B and D B Boyd itors) Reviews in Computational Chemistry Volume 11. New York, VCH Publishers, pp. 1-66. 

Mnreko MA. Recent advances in ligand design methods. In Lipkowitz KB, Boyd DB, editors. Reviews in Computational Chemistry, Vol. 11. New York Wiley-VCH, 1997. p. 1-66. 

Mark A. Murcko, Recent Advances in Ligand Design Methods. 

Brooijmans, N., and Kuntz, 1. Principles and methods of docking and ligand design. Methods Biochem. Anal. 2003, 44, 443-476. 

K. Gubemator and H. J. Bohm. 1998. Structure-Based Ligand Design, Methods and Principles in Medicinal Chemistry. Weinheim Wiley-VCH. 

In the second example, in which desolvation influences were considered, Reddy et al. used a computer-assisted ligand design method that combines molecular mechanics, molecular dynamics, FEP calculations, synthesis, and biochemical testing of peptidomimetic inhibitors, plus crystallographic structure determination of the protein-inhibitor complexes. This combination of techniques successfully led to the design of novel inhibitors for the HIV-1 protease enzyme. This study involved a large set of molecules whose relative binding affinities, predicted via the FEP method prior to synthesis, were later confirmed by experimental measurements. 

The slippery slope How should we define a ligand design method For example, are fragment location techniques bona fide de novo design methods or simply a prerequisite for de novo design ... 

When comparing ligand design methods, there are many questions to be... 

DETAILS OF SPECIFIC DE NOVO LIGAND DESIGN METHODS... 

Details of Specific De Novo Ligand Design Methods 19... 

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