In this paper, we propose a new computational approach to characterize MB-MC designed to capture the conditions experienced in condensed matter via the application four-body external potentials that affects torsional (proper dihedrals) and out-of-plane deformations (improper dihedrals). Our approach demonstrates the importance of many-body deformations on the activation energy of mechanophore isomerization (spiropyran) and the thermal decomposition of 1,3,5-trinitro-2,4,6-triaminobenzene (TATB). In the first example, we couple a four-body deformation around the spiro atom and apply the widely used CoGEF 31 method to load the mechanophore. We show that straining the central torsional angle by ~50 reduces the energy barrier associated with the mechanical activation of the mechanophore by a factor of two. The second example couples external many-body potentials that mimic the molecular strains observed under shock loading using reactive molecular dynamics in the molecular crystal TATB. A Kissinger analysis of the MD simulations shows marked changes in chemical kinetics and decomposition paths that can explain previous inconsistencies between mechanical and thermal insults in this class of materials . Importantly, this second example cannot be tackled at all with any prior approaches.