Molecular Dynamics Simulations Enforcing Nonperiodic Boundary Conditions: New Developments and Application to the Solvent Shifts of Nitroxide Magnetic Parameters

Multiscale methods combining quantum mechanicsand molecular mechanics (QM/MM) have become the mostsuitable and effective strategies for the investigation of thespectroscopic properties of medium-to-large size chromophoresin condensed phases. In this context, we are developing a novelworkflow aimed at improving the generality, reliability, and ease ofuse of the available computational tools. In this paper, we reportour latest developments with specific reference to a generalprotocol based on atomistic simulations, carried out undernonperiodic boundary conditions (NPBC). In particular, we addto our in house MD engine a new efficient treatment of meanfieldelectrostatic contributions to energy and forces, together with the capability of performing the simulations either in the canonical(NVT) or in the isothermal-isobaric (NPT) ensemble. Next, we provide convincing evidence that the NBPC approach enhanced byspecific tweaks for rigid body propagation, allows for the simulation of solute-solvent systems with a minimum number of degrees offreedom and large integration time step. After its validation, this new approach is applied to the challenging case of solvatochromiceffects on the electron paramagnetic resonance (EPR) spectrum of a prototypical nitroxide radical. To this end, we propose andvalidate also an automated protocol to extract and weight simulation snapshots, making use of a continuous description of thestrength of solute-solvent hydrogen bridges. While further developments are being worked on, the effectiveness of our approach,even in its present form, is demonstrated by the accuracy of the results obtained through an unsupervised approach characterized bya strongly reduced computational cost as compared to that of conventional QM/MM models, without any appreciable deteriorationof accuracy.