Energy minimization and molecular dynamics studies of Asn-102 elastase

Area of Science:

• Biochemistry
• Structural Biology
• Computational Chemistry

Background:

• The Asn-102 PPE (D102N mutant) is a key enzyme variant.
• Understanding its isomeric forms is crucial for elucidating catalytic mechanisms.
• Previous studies utilized various techniques to probe enzyme structure and function.

Purpose of the Study:

• To investigate the structural and energetic properties of four isomeric forms of the Asn-102 PPE (D102N mutant).
• To compare the active site conformations and hydrogen bonding patterns with the native enzyme.
• To discuss the pH-dependent activity of the D102N derivative.

Main Methods:

• Energy minimization (EM) and molecular dynamics (MD) simulations were employed.
• MD simulations were performed for 175 ps per form, totaling 700 ps for approximately 2500 atoms.
• Analysis focused on active site conformations and hydrogen bond patterns.

Main Results:

• The His-57 N epsilon-protonated forms were found to be more stable than the N delta-protonated forms.
• The active site region of the most stable form closely resembles that of the D102N rat trypsin enzyme.
• Detailed conformations and hydrogen bond networks were elucidated for each isomer.

Conclusions:

• Protonation state of His-57 significantly influences the stability of Asn-102 PPE (D102N mutant) isomers.
• The structural similarity to D102N rat trypsin provides a basis for understanding its enzymatic behavior.
• Further discussion on pH-dependent activity is warranted based on these structural findings.