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Position

Fragment Positioning

General remarks

The option 'p' of the menu 'cnf' allows to position molecules (fragments) in the active site of a enzyme or the cavity of a receptor. It may be (mis-)used to dock larger and flexible structures, but other programs are better optimized for that purpose. For a basic, though somewhat outdated, general description see the first section of the Lego Tutorial.
The algorithm positions a fragment at various places (determined by the positions entry) in various initial orientations (and, optionally, in various initial conformations). Every initial position of the fragment is subjected to a MAB force field minimization in which a background entry is also present, though with fixed atomic positions. The lowest-energy results of these minimizations are kept in a conformation library. Clearly, if one tries to position larger molecules with this algoritm (full docking), they may entangle with the environment enty. This may in unfavorable cases lead to a hang-up of the minimizer!
We use the B-chain of dihydrofolatereductase as cavity and the diaminopyrimidine fragment of trimethoprim as the fragment to be positioned. The corresponding files, 4dfr.pdb, and trimethoprim.mab can be found in the moloc/dat directory.

Preliminary Actions

An example file 4dfr_B_env.mab can be found in the moloc/dat directory.

Generating the Entry of Initial Positions

Generate Library of Positioned Fragments

Generate a Further Library

The preparations of the previous sections can be reused to produce further libraries of positioned structures. We demonstrate this with the example of the entire trimethoprim structure.

Analyze Positions

The generated positions for a conformation library and can be analyzed completely analogous to normal conformations (see section 'Analyze conformations' of the Conformation Analysis Tutorial).
A few trivial tips: