Plasminogen Activator Inhibitor-1 (PAI-1) is a key protein used in fibrinolysis, the process by which blood clots are broken down in the body. In some cases it is desirable to inhibit PAI-1, thus increasing the rate of fibrinolysis. Previous research has shown that polyphenolic short chain compounds can be effective inhibitors of PAI-1. In this work, we determine an appropriate computational methodology to analyze the interaction of small molecule inhibitors with the binding site of PAI-1. Specifically, we use a QM/MM approach to optimize the position of several inhibitors in the binding site, followed by an NBO analysis of the interactions between each inhibitor and the active site residues.  The results indicate that at least six residues are involved in binding the inhibitors including arginine, lysine, proline, and aspartate.  The efficacy of the inhibitors is also correlated to the strength of interaction with the binding site.

Computational study of PAI-1 and its interactions with an inhibitor

244th National Meeting (2012)

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