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Building

Building a Small Molecule (Peptide)

Although small molecules can be built from scratch, a much more frequent case is that an existing structure is modified to anticipate possible chemical modifications. We will start from methotrexate and rebuild it to arrive at trimethoprim, a alternative dihydrofolate reductase inhibitor.

Delete Redundant Atoms:

Add New Atoms and Fragments:

Adjust Initial Conformation Manually:

Check Silent Hydrogens:

Optimize the Conformation within the Fixed Protein:

Save the New Structure together with the Protein onto a .pdb File

You are strongly discouraged to store structures on .pdb-type files, just to save your work for later continuation, because impotant information on non-protein structures cannot be stored, most importantly, the atomic H-counts which determine the molecular topology. However, there are programs which require this file type.
The format of a .pdb file is somewhat tricky. Moloc will write a correct file, if the entries are properly prepared. This requires the following steps: In case the ligand is covalently bound, the procedure has to be analogous, i.e. the ligand has to be built beforehand as a separate entry, than to be added to the protein entry as a new heterogen. Only then can the covalent connection be made.
The (not working!) alternative would be to build the complex by extending the covalently bound residue with the ligand atoms. Although this leads to the same topology, the monomer specification is different and not compatible with Brookhaven rules. This, because upon extending a residue Moloc changes the whole residue to type 'UNK' (unknown but still in the chain and, thus, not a heterogen). Removing atoms from a residue is, of course, allowed. It simply yields a incomplete residue.