Computational Drug Discovery and Design

4 Case Studies

Various fragment based drug designing approaches have shifted the

focus of pharmaceutical industries and academia from high

throughput screening to structural biology based designing of

drug molecules. Several successful attempts of de novo designing

of ligand molecules have already been published in the last few

years. Some of them are discussed here to give a brief overview of

how one proceeds with drug designing studies.

4.1 Structure-Based
De Novo Design
Against COX-2

Cyclooxygenase-2 (COX-2) is an enzyme that catalyzes the forma-

tion of prostaglandins in a two-step process and has different active

sites to perform its cyclooxygenase and peroxidase activity. Two

isoforms of COX enzyme, COX-1 and COX-2, share high struc-

tural homology but engage in different roles. To be precise, COX-1

is involved in keeping housekeeping functions, whereas COX-2

Table 1
List of de novo structure-based and ligand-based lead designing software

Structure-based approach Ligand-based approach

Building

block Scoring function

Building

block Scoring function

LigMerge Fragment – NEWLEAD – –

LigBuilder Fragment Empirical scoring

function

PhDD Fragments Pharmacophore model

LEGEND Atom Force field TOPAS –

LUDI Fragment Empirical scoring

function

CoG – –

SPROUT Fragment SASA, electrostatic Flux – –

BREED Fragment – LEA3D Fragment Composite fitness function

AlleGrow Fragment Empirical and force

field

Globus Fragment All-atom-pairs-shortest-

path descriptor

SYNOPSI

S

Fragment Empirical Nachbar Fragment Target specific QSAR

iScreen Fragment LEA3D’s scoring

function

PRO_LIGAND – –

DycoBlock Fragment Force field and

SASA

SkelGen – –

GANDI Fragment Force field

Various software have been developed based on different objectives, and hence, their starting building material and the
scoring functions have also been mentioned

134 Shashank P. Katiyar et al.