Molecular modeling of bifunctional chelate peptide conjugates. 1. Copper and indium parameters for the AMBER force field

In this work we describe the development of parameters for In(III) and Cu(I I) for the AMBER* force field as found in the modeling package MacroModel. These parameters were developed using automated procedures from a combinati on of crystallographic structures and ab initio calculations. The new param eters were added in the form of AMBER* substructures containing specific me tal-ligand parameters to the existing force field. These new parameters hav e produced results in good agreement with experiment without requiring addi tional changes to the existing AMBER* parameters. These parameters were the n utilized to examine the conformational effects caused by the conjugation of InDTPA (DTPA = diethylenetriaminepentaacetic acid) and CuDOTA (DOTA 1,4, 7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) to the cyclic octapep tide octreotide.