Exploitation of Conformational Dynamics in Imparting Selective Inhibition for Related Matrix Metalloproteinases Kiran V. Mahasenan Maria Bastian Ming Gao Emma Frost Derong Ding Katerina Zorina-Lichtenwalter John Jacobs Mark A. Suckow Valerie A. Schroeder William R. Wolter Mayland Chang Shahriar Mobashery 10.1021/acsmedchemlett.7b00130.s001 https://acs.figshare.com/articles/journal_contribution/Exploitation_of_Conformational_Dynamics_in_Imparting_Selective_Inhibition_for_Related_Matrix_Metalloproteinases/4964759 Matrix metalloproteinases (MMPs) have numerous physiological functions and share a highly similar catalytic domain. Differential dynamical information on the closely related human MMP-8, -13, and -14 was integrated onto the benzoxazinone molecular template. An <i>in silico</i> library of 28,099 benzoxazinones was generated and evaluated in the context of the molecular-dynamics information. This led to experimental evaluation of 19 synthesized compounds and identification of selective inhibitors, which have potential utility in delineating the physiological functions of MMPs. Moreover, the approach serves as an example of how dynamics of closely related active sites may be exploited to achieve selective inhibition by small molecules and should find applications in other enzyme families with similar active sites. 2017-05-01 00:00:00 Conformational Dynamics enzyme families benzoxazinone function molecular-dynamics information Related Matrix Metalloproteinases Matrix metalloproteinases site silico library MMP