It has been found that certain platinum compounds act as
anticancer drugs or as agents to cleave proteins. Molecular mechanics calculations are utilized to predict the
interactions of new compounds with proteins or to interpret experimental data
for known compounds. We have utilized a
modified AMBER force field and have added additional parameters that permit the
major platinum-methionine complexes to be modeled.< Molecular mechanics analysis of
Pt(Me<sub>4</sub>en)(methionine)<sub>2</sub> and
Pt(Et<sub>2</sub>en)(methionine)<sub>2</sub> complexes
(Me<sub>4</sub>en = N,N,N',N'-tetramethylethylenediamine;
Et<sub>2</sub>en = N,N-diethylethylenediamine), in which the
methionine residues are coordinated via the sulfur atom, revealed significant
steric clashes; experimental studies have confirmed that such complexes do not
form. Chelates in which a single
methionine residue coordinates to the platinum via the sulfur atom and either a
nitrogen atom or an oxygen atom generally have less steric hindrance. The calculations provide an interpretation
for many results that have been observed experimentally.