Energy flow and intersubunit signalling in GSAM: A non-equilibrium molecular dynamics study

Area of Science:

• Biophysics
• Enzymology
• Computational Biology

Background:

• Glutamate-1-semialdehyde aminomutase (GSAM) is crucial for chlorophyll biosynthesis.
• GSAM exhibits negative cooperativity in its active site gating loops, suggesting complex functional dynamics.

Purpose of the Study:

• To identify vibrational energy transport pathways within GSAM.
• To understand the role of these pathways in allosteric communication and coordinating functional dynamics, particularly negative cooperativity.

Main Methods:

• Non-equilibrium molecular dynamics (MD) simulations using the GROMACS package.
• Atomistic simulations of thermal diffusion by imposing temperature gradients across the GSAM enzyme.
• Monitoring residue temperatures over time to map energy flow.

Main Results:

• Energy deposition occurs along discrete residue chains, many with specific functional roles.
• Thermal linkages between these chains were mapped, establishing pathways for vibrational energy flow.
• Pathways were identified connecting active sites through conserved, hydrogen-bonded residues.

Conclusions:

• Vibrational energy flow occurs through specific residue networks in GSAM.
• These pathways act as communication channels, linking active sites and influencing gating loop dynamics.
• The findings provide insights into the allosteric mechanisms coordinating enzyme function.