Computational Tools for In Silico Fragment-Based Drug Design

Title:Computational Tools for In Silico Fragment-Based Drug Design

Volume: 12 Issue: 17

Author(s): Jeremie Mortier, Christin Rakers, Raphael Frederick and Gerhard Wolber

Affiliation:

Keywords: Fragment-based design, libraries, software, molecular modelling, rule of three, fragment linkage

Abstract: Fragment-based strategy in drug design involves the initial discovery of low-molecular mass molecules. Owing to their small-size, fragments are molecular tools to probe specific sub-pockets within a protein active site. Once their interaction within the enzyme cavity is clearly understood and experimentally validated, they represent a unique opportunity to design potent and efficient larger compounds. Computer-aided methods can essentially support the identification of suitable fragments. In this review, available tools for computational drug design are discussed in the frame of fragmentbased approaches. We analyze and review (i) available commercial fragment libraries with respect to their properties and size, (ii) computational methods for the construction of such a library, (iii) the different strategies and software packages for the selection of the fragments with predicted affinity to a given target, and (iv) tools for the in silico linkage of fragments into an actual high-affinity lead structure candidate.

Cite this article as:

Mortier Jeremie, Rakers Christin, Frederick Raphael and Wolber Gerhard, Computational Tools for In Silico Fragment-Based Drug Design, Current Topics in Medicinal Chemistry 2012; 12 (17) . https://dx.doi.org/10.2174/156802612804547371