Matrix metalloproteinase-1 (MMP-1) is a Zn(II) dependent endopeptidase involved in the degradation of collagen, the most abundant structural protein in the extracellular matrix of connective tissues and the human body. Herein we performed a multilevel computational analysis including molecular dynamics (MD), combined quantum mechanics/molecular mechanics (QM/MM), and quantum mechanics (QM) calculations to characterize the structure and geometry of the catalytic Zn(II) within the MMP-1 protein environment in comparison to crystallographic and spectroscopic data. The substrate's removal fine-tuned impact on the conformational dynamics and geometry of the catalytic Zn(II) center was also explored. Finally, the study examined the effect of substituting catalytic Zn(II) by Co(II) on the overall structure and dynamics of the MMP-1 • THP complex and specifically, on the geometry of the catalytic metal center. Overall, our QM/MM and QM studies were in good agreement with the MM description of the Zn(II) centers in the MD simulations.

The front cover artwork is provided by Dr. Karabencheva‐Christova's group at Michigan Technological University. The image shows the multilevel molecular dynamics (MD), quantum mechanics/molecular mechanics (QM/MM) and quantum mechanics (QM) study on matrix metalloproteinase‐1 (MMP‐1). Read the full text of the Article at 10.1002/cphc.202100680.

The Front Cover shows the multilevel molecular dynamics (MD), quantum mechanics/molecular mechanics (QM/MM) and quantum mechanics (QM) study on matrix metalloproteinase‐1 (MMP‐1). More information can be found in the Article by Tatyana G. Karabencheva‐Christova and co‐workers.