Kinetic and molecular modeling of nucleoside and nucleotide inhibition of malate dehydrogenase.

We studied the inhibition of mitochondrial malate dehydrogenase (mMDH) by the nucleotides cAMP, AMP, ADP, ATP. The experimental kinetic studies showed that the nucleotides were competitive inhibitors and that cAMP was probably the most potent inhibitor. To explain these observations, we used molecular modeling to determine the location, orientation, and relative binding energy of the nucleotides to mMDH.

Procedure for selecting starting conformations for energy minimization of nucleosides and nucleotides.

The purpose of this study was to carry out a thorough search of the conformational space of various adenine-containing nucleotides, applying a previously published searching procedure, known as the representative method. This method, which reduces the number of starting conformations required to explore all the important regions of conformational space, appears to be successful in finding all (or nearly all) the putative low-energy conformations of each molecule.