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The Perturbed Matrix Method (PMM) approach to be used in combination with Molecular Dynamics (MD) trajectories (MD-PMM) has been recoded from scratch, improved in several aspects, and implemented in the Gaussian suite of programs for allowing a user-friendly and yet flexible tool to estimate quantum chemistry observables in complex systems in condensed phases. Particular attention has been devoted to a description of rigid and flexible quantum centers together with powerful essential dynamics and clustering approaches. The default implementation is fully black-box and does not require any external action concerning both MD and PMM sections. At the same time, fine-tuning of different parameters and use of external data are allowed in all the steps of the procedure. Two specific systems (Tyrosine and Uridine) have been reinvestigated with the new version of the code in order to validate the implementation, check the performances, and illustrate some new features.

Background The mechanism of how the hydrophilic threefold channel (C3) of ferritin nanocages facilitates diffusion of diverse metal ions into the internal cavity remains poorly explored. Methods Computational modeling and free energy estimations were carried out on R. catesbeiana H´ ferritin. Transit features and associated energetics for Fe2+, Mg2+, Zn2+ ions through the C3 channel have been examined. Results We highlight that iron conduction requires the involvement of two Fe2+ ions in the channel. In such doubly occupied configuration, as observed in X-ray structures, Fe2+ is displaced from the internal site (stabilized by D127) at lower energetic cost. Moreover, comparison of Fe2+, Mg2+ and Zn2+ transit features shows that E130 geometric constriction provides not only an electrostatic anchor to the incoming ions but also differentially influence their diffusion kinetics. Conclusions Overall, the study provides insights into Fe2+ entry mechanism and characteristic features of metal-protein interactions that influence the metal ions passage. The dynamics data suggest that E130 may act as a metal selectivity gate. This implicates an ion-specific entry mechanism through the channel with the distinct diffusion kinetics being the discriminating factor. General Significance Ferritin nanocages not only act as biological iron reservoirs but also have gained importance in material science as template scaffolds for synthesizing metal nanoparticles. This study provides mechanistic understanding on the conduction of different metal ions through the channel.

Some years ago we developed a theoretical-computational hybrid quantum/classical methodology, the Perturbed Matrix Method (PMM), to be used in conjunction with molecular dynamics simulations for the investigation of chemical processes in complex systems, that proved to be a valuable tool for the simulation of relevant experimental observables, e.g., spectroscopic signals, reduction potentials, kinetic constants. In typical PMM calculations the quantum sub-part of the system, the quantum centre, is embedded into an external perturbing field providing a perturbation operator explicitly calculated up to the dipolar terms. In this paper we further develop the PMM approach, beyond the dipolar terms in the perturbation operator expansion, by including explicitly the quadrupolar terms and/or by expanding the perturbation operator on each atom of the quantum centre. These different levels of the perturbation operator expansion, providing different levels of theory, have been tested by calculating three different spectroscopic observables: the spectral signal of liquid water and aqueous benzene due to the lowest energy electronic excitation and the infrared amide I band of aqueous trans-N-methylacetamide. All the systems tested show that, even though the previous PMM level of theory is already capable of reproducing the main features of the spectral signal, the higher levels of theory improve the quantitative reproduction of the spectral details.

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.

The UV-vis spectrum of Tyrosine and its response to different backbone protonation states have been studied by applying the Perturbed Matrix Method (PMM) in conjunction with molecular dynamics (MD) simulations. Herein, we theoretically reproduce the UV-vis absorption spectrum of aqueous solution of Tyrosine in its zwitterionic, anionic and cationic forms, as well as of aqua-p-Cresol (i.e., the moiety that constitutes the side chain portion of Tyrosine). To achieve a better accuracy in the MD sampling, the Tyrosine Force Field (FF) parameters were derived de novo via quantum mechanical calculations. The UV-vis absorption spectra are computed considering the occurring electronic transitions in the vertical approximation for each of the chromophore configurations sampled by the classical MD simulations, thus including the effects of the chromophore semiclassical structural fluctuations. Finally, the explicit treatment of the perturbing effect of the embedding environment permits to fully model the inhomogeneous bandwidth of the electronic spectra. Comparison between our theoretical-computational results and experimental data shows that the used model captures the essential features of the spectroscopic process, thus allowing to perform further analysis on the strict relationship between the quantum properties of the chromophore and the different embedding environments. © 2018 Wiley Periodicals, Inc.