Tailor-made computational protocols for precise characterization of small biological building blocks using QM and MM approaches

Computational modeling involving Quantum Mechanics (QM) and Molecular Mechanics (MM) calculations are widely utilized to unveil the atomic-molecular properties that underpin their inherent characteristic features. The choice over the either of the QM and MM methods or a multiscale composite approach is driven by the target property of interest, and of course, the molecular size. Often, tailor-made schemes need to be devised to match the specific study purpose. Herein, we provide a perspective of these approaches addressing their effectiveness in terms of the delicate balance between the accuracy and computational feasibility. We focus on representative examples to highlight how different approaches can be fruitfully exploited for modeling the conformational landscape, and possibly, the spectroscopic behavior of biochemical molecules, especially amino acids building blocks.