Convergent Protocols for Computing Protein-Ligand Interaction Energies Using Fragment-Based Quantum Chemistry.

ABSTRACT: Fragment-based quantum chemistry methods offer a means to sidestep the steep nonlinear scaling of electronic structure calculations so that large molecular systems can be investigated using high-level methods. Here, we use fragmentation to compute protein-ligand interaction energies in systems with several thousand atoms, using a new software platform for managing fragment-based calculations that implements a screened many-body expansion. Convergence tests using a minimal-basis semiempirical method (HF-3c) indicate that two-body calculations, with single-residue fragments and simple hydrogen caps, are sufficient to reproduce interaction energies obtained using conventional supramolecular electronic structure calculations, to within 1 kcal/mol at about 1% of the computational cost. We also

SUBMITTER: Bowling PE 

PROVIDER: S-EPMC11950710 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature