Assessing AMBER and UNRES Force Fields on the Energy Landscape of Bovine Pancreatic Trypsin Inhibitor

Abstract

Biological complexity emerges from the collective behaviour of proteins, whose folding and conformational dynamics are directly governed by the underlying potential energy surface. Here, we compare the potential energy landscapes of bovine pancreatic trypsin inhibitor (BPTI) obtained with the all-atom AMBER force field and the coarse-grained UNRES potential. For the native triply disulphide-bonded state of BPTI, both models sample predominantly folded, native-like conformations with relatively small structural deviations from the crystallographic structure, though UNRES explores structures with a broader range of RMSDs compared to experimental structure, radii of gyration, and solvent-accessible surface areas. Using comparable CPU time, UNRES generates a more diverse set of minima and transition states, yielding a more extensively sampled landscape with a globally similar topology. Together, these results highlight how all-atom and coarse-grained potentials differ in the representation of protein energy landscapes, while retaining consistent global features for a highly constrained, disulphide-rich protein such as BPTI.