Protein Loop Construction with MacroModel

Before analyzing how a given protein-ligand pair will interact, you may want to refine the protein structure. This commonly involves examining the structure of loops—short sequences of amino acids which typically occur on the surface of the protein, but in the middle of the protein sequence.

The reasons for refining a protein structure include:

• The structure of this portion of the protein was not well-resolved.
• The conformation of the loop changed upon solvation.

In addition, when working with enzymes, you may want to examine how the structure of the loop changes as you change the sequence in the loop.

The MacroModel LOOP tool is a conformational search method for protein loops. It generates a variety of structures that are both diverse and geometrically appropriate for the protein loop, and minimizes the energy of these structures. LOOP functions in much the same manner as MCMM, and is used in conjunction with the MINI, MCOP, MSYM, and LPOP opcodes. LOOP is best used in conjunction with other methods, like LLMOD, to sample the loop structures more thoroughly. For more information on LOOP, see the LOOP opcode description.