Searching for the Lowest Energy Conformation of Substrates in the Carboxypeptidase A Active Site Using Monte Carlo/Energy Minimization Techniques

More than fifteen substrates of carboxypeptidase A (CPA) have been “docked” to the active site of the enzyme and searched for the lowest energy conformation of the substrates bound to the active site. The method employed combines Monte Carlo procedures with energy minimization (MC/EM procedures). The distances of P1′–P3to S1′–S3were measured. The computational results are consistent with the proposed binding interactions of CPA and its substrates and also with the promoted-water pathway of CPA catalysis. This study has demonstrated that MC/EM procedures are very useful for searching the conformations of substrates available in the active site of the enzyme.