2024 DOCK GA tutorial 1 with 1NDV
Contents
I. Introduction
A genetic algorithm is a form of de novo design. This form of de novo grows new molecules through a process of evolutionary growth that includes crossover of parent molecules, mutations, and a "natural selection" process. Crossover occurs when two parent molecules have rotatable bonds in the same area of the binding site. This will exchange the fragments between the parents, and creature two new offspring. There are 4 different mutations that can occur during genetic growth. There can be deletion of an existing fragment, addition of a new fragment, substitution of a terminal fragment, and replacement of a linker fragment. After crossover and mutation occurs the new molecules are scored and a select amount are carried over into the next stage of growth. In this tutorial will be using the Elitism elimination method, so only the top scoring molecules will move on to the next generation.
II. Fragment Library Generation for 1NDV
Fragment Libraries
In order for the GA to work, we first need to produce a large and diverse fragment library. Make a directory to run the GA in called "1NDV_GA". Now enter that directory and make a new directory named "fraglib". This is where we will build our fragment library. Create a new file for the fragment library and use it as input for dock6 so we can interactively build the library using the following commands.
touch 1NDV.fraglib dock6 -i 1NDV.fraglib
Now answer the prompts using the responses below as a guide.
conformer_search_type flex write_fragment_libraries yes fragment_library_prefix 1ndv.fraglib fragment_library_freq_cutoff 1 fragment_library_sort_method freq fragment_library_trans_origin no use_internal_energy no ligand_atom_file /gpfs/projects/AMS536/2024/students/group_2_1NDV/dock_screen/001.structure/1ndv_ligand_only_H_charge.mol2 limit_max_ligands no skip_molecule no read_mol_solvation no calculate_rmsd no use_database_filter no orient_ligand no bump_filter no score_molecules no atom_model all vdw_defn_file /gpfs/projects/AMS536/zzz.programs/dock6.10/parameters/vdw_AMBER_parm99.defn flex_defn_file /gpfs/projects/AMS536/zzz.programs/dock6.10/parameters/flex.defn flex_drive_file /gpfs/projects/AMS536/zzz.programs/dock6.10/parameters/flex_drive.tbl ligand_outfile_prefix 1ndv.frag.output write_orientations no num_scored_conformers 1 rank_ligands no
