Computational Drug Discovery and Design

includes all the information required to runPOCKET. Simple

command line for runningPOCKETis:

#Pocket parameter_file.index

Parameter file contains information about the input files,

i.e., LIGAND_FILE (Mol2 file of ligand of target protein),

RECEPTOR_FILE (PDB file of target protein) and PARA-

METER_DIRECTORY (path to directory “parameter” that

includes all force field parameters used by LigBuilder). It also

includes information about the program’s output such as

POCKET_ATOM_FILE (includes information about atoms

of the binding pocket), POCKET_GRID_FILE (contain infor-

mation about grids inside the binding pocket) and KEY_SI-

TE_FILE (describes the key interaction sites of binding

pocket).

2.Generation of seed from reference molecules

Successful drug discovery initially requires identification of

seed molecules for generation of lead compounds. Preparation

of seed is generally done by identification of the substructures

present in the active compounds. These desirable molecules are

not present in fragment libraries. The seed molecules are

arranged in a hierarchical manner to traverse the chemical

space completely. For this purpose a reference structure that

already has its biological activity established is used as an input.

The seeds are generated by the fragmentation of the reference

structure. This generation of seed molecules gives rise to an

initial set comprising of individual structures.

3.Construction of ligand molecule through fragment growing

GROW, a LigBuilder module, uses the seed structures and

binding pocket site information for the generation of ligand

molecule by growing seed structure through addition of frag-

ments from fragment library. It employs genetic algorithm for

evolution of fragments into lead-like molecules. Addition of

fragments to seed molecules yields initial structures that are

manipulated by fragment mutation or crossover for several

generations, to yield lead molecule similar to reference mole-

cule but with different scaffold and better interactions with

target molecule [56, 57]. Command line for runningGROW

is:

#grow Parameter_file_for_grow.index

Parameter file forGROWincludes information about all

the input files, output files, and setting up manipulations

related to growing, linking and mutation. It also includes

parameters required for running genetic algorithms like

132 Shashank P. Katiyar et al.