Structure-function-dynamics of α-chymotrypsin based conjugates as a function of polymer charge

Area of Science:

• Bioconjugation Chemistry
• Computational Biochemistry
• Polymer Science

Background:

• Developing predictive tools for protein-polymer conjugates is crucial for enhancing their activity and stability.
• Structure-function-dynamics relationships are vital but challenging to elucidate due to complex protein-polymer interactions.
• Nanoscale interaction probing is difficult experimentally, necessitating advanced computational methods.

Purpose of the Study:

• To investigate the impact of polymer charge on protein dynamics and conformation using molecular dynamics (MD) simulations.
• To understand how different polymer types influence protein structure and function at an atomic level.
• To establish structure-function-dynamics relationships for protein-polymer conjugates.

Main Methods:

• Atomistic molecular dynamics (MD) simulations were employed.
• Studied alpha-chymotrypsin (CT) densely conjugated with zwitterionic, positively charged, and negatively charged polymers.
• Analyzed protein-polymer interactions, protein dynamics, and conformational changes.

Main Results:

• Polymer flexibility influenced interaction extent and location on the protein surface.
• Negatively charged polymers induced structural deformations in CT's substrate binding pocket and active site.
• Zwitterionic and positively charged polymers did not cause significant structural deformations.
• Polymer attachment displaced water from the protein surface, with hydration correlating to the Hofmeister series.

Conclusions:

• The charge of conjugated polymers significantly impacts protein structure and dynamics.
• Negatively charged polymers pose a risk of altering enzyme active site integrity.
• Computational MD simulations provide atomic-level insights into protein-polymer conjugate behavior, aiding rational design.