A Systematic Computational Protocol for Deconstructing Non-Covalent Interactions: BerchNCI 1.0

Abstract

Non-covalent interactions constitute the fundamental organizing principles of supramolecular assemblies; however, the accurate modeling of these subtle, dispersion-driven forces remains a formidable challenge in theoretical chemistry. In this work, we formally propose the Berchmans Protocol for Modelling Non-Covalent Interactions 1.0 (BerchNCI 1.0), a comprehensive, hierarchical computational workflow designed to decipher the electronic anatomy of NCIs with benchmark precision. The BerchNCI 1.0 protocol systematizes the characterization of weak interactions by integrating geometry optimization via dispersion-corrected functionals with a range of analytical descriptors. This strategy employs the Non-Covalent Interaction index, Quantum Theory of Atoms in Molecules, and the Independent Gradient Model based on Hirshfeld partition to visualize and quantify interaction topologies. The physical driving forces of molecular association, including electrostatics, dispersion, and Pauli repulsion, are dissected using Local Energy Decomposition analysis. Uniquely, this protocol extends beyond static analysis by incorporating ab initio Molecular Dynamics to assess the thermodynamic stability and temporal evolution of these assemblies. We present BerchNCI 1.0 as a standardized methodology for resolving competitive interactions and rationalizing molecular recognition across diverse chemical environments.