Gi\Delta \Delta G_i penalizes destabilizing mutations in proportion to thermodynamic cost.
This allows for a temperature-tuned simulation regime, akin to simulated annealing, where:
High system entropy (early stages) allows broad mutation exploration,
Low entropy (later stages) sharpens toward local optima or functional innovations.
3. Bifurcation and Phase Transition Analogies
As mutations accumulate and interaction levels shift, the system can undergo bifurcations---nonlinear jumps between structural configurations or functional states. These bifurcations are modeled as phase transitions in the system:
From unfolded to folded,
From inactive to catalytically competent,
From narrow to broad substrate spectrum.
The use of thermodynamic potentials and energy landscape topology allows us to simulate not just steady-state function, but adaptive jumps, which mirror real-life phenomena such as promiscuous activity leading to neo-functionalization.
4. Coupling Mutation, Selection, and Thermodynamic Recalibration
