Trypsin-benzamidine complex

One of the most critical technical issues regarding LIE type of calculations seems to be the treatment of electrostatic interactions, at least for charged ligands. These problems were discussed in Ref. 19 using the trypsin-benzamidine complex as an illustration. The starting point was then that one should expect, or require, that the electrostatic free energies calculated with the LIE method have some physical meaning, even in... 

Using this approach, Bizzozero and Zweifel (9) and Bizzozero and Dutler (10) have constructed molecular models of two intermediates (an enzyme-substrate complex and a tetrahedral intermediate) by appropriate modification of the models of stable enzyme-species. The stable enzyme-species used (15, 16) are trypsin-benzamidine complex (TR-B) (17), trypsin-pancreatic trypsin inhibitor complex (TR-PTI) (18, 19) and tosyl-chymotrypsin (Tos-CHT) (20) which are related to enzyme substrate complex, tetrahedral intermediate and acyl-enzyme respectively. 

J. W. Essex, D. L. Severance, J. Tirado-Rives, and W. L. Jorgensen, /. Phys. Chem. B, 101, 9663 (1997). Monte Carlo Simulations for Proteins Binding Affinities for Trypsin-Benzamidine Complexes Via Free-Energy Perturbations. 

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