How Accurate Are QM/MM Models?

The Journal of Physical Chemistry A, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 4, 2024

Despite the success and widespread use of QM/MM methods in modeling (bio)chemically important processes, their accuracy is still not well understood. A key reason because these are ultimately approximations to direct QM calculations very large systems, which impractical perform most cases. We highlight recent progress toward development realistic model systems where it possible obtain full reference data directly systematically evaluate effectiveness different generation schemes. These highly flexible can be tailored probe sensitivity a reaction types simulation parameters such as pairing MM potentials, region size, composition. It envisaged that this strategy could used validate schemes spur more robust models future.

Language: Английский

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Pathways to a Shiny Future: Building the Foundation for Computational Physical Chemistry and Biophysics in 2050

ACS Physical Chemistry Au, Journal Year: 2024, Volume and Issue: 4(4), P. 302 - 313

Published: April 4, 2024

In the last quarter-century, field of molecular dynamics (MD) has undergone a remarkable transformation, propelled by substantial enhancements in software, hardware, and underlying methodologies. this Perspective, we contemplate future trajectory MD simulations their possible look at year 2050. We spotlight pivotal role artificial intelligence (AI) shaping broader computational physical chemistry. outline critical strategies initiatives that are essential for seamless integration such technologies. Our discussion delves into topics like multiscale modeling, adept management ever-increasing data deluge, establishment centralized simulation databases, autonomous refinement, cross-validation, self-expansion these repositories. The successful implementation advancements requires scientific transparency, cautiously optimistic approach to interpreting AI-driven analysis, mindset prioritizes knowledge-motivated research alongside AI-enhanced big exploration. While history reminds us technological progress can be unpredictable, Perspective offers guidance on preparedness proactive measures, aiming steer most beneficial direction.

Language: Английский

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Constrained nuclear-electronic orbital QM/MM approach for simulating complex systems with quantum nuclear delocalization effects incorporated

Chemical Physics Reviews, Journal Year: 2024, Volume and Issue: 5(4)

Published: Oct. 9, 2024

The hybrid quantum mechanics/molecular mechanics (QM/MM) approach, which combines the accuracy of QM methods with efficiency MM methods, is widely used in study complex systems. However, past QM/MM implementations often neglect or face challenges addressing nuclear effects, despite their crucial role many key chemical and biological processes. Recently, our group developed constrained nuclear-electronic orbital (CNEO) theory, a cost-efficient approach that accurately addresses especially delocalization effects. In this work, we integrate CNEO through electrostatic embedding scheme apply resulting to two hydrogen-bonded complexes. We find both solvation effects significantly impact hydrogen bond structures dynamics. Notably, glutamic acid–glutamate complex, mimics common low barrier systems, predicts nearly equal proton sharing between residues. With an accurate description environmental promising new for simulating

Language: Английский

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Protein network centralities as descriptor for QM region construction in QM/MM simulations of enzymes

Physical Chemistry Chemical Physics, Journal Year: 2023, Volume and Issue: 25(30), P. 20183 - 20188

Published: Jan. 1, 2023

The construction of a suitable QM region is the most crucial step in setting up hybrid quantum mechanics/molecular mechanics (QM/MM) simulations for enzymatic reactions. should ideally include all important amino acids residues, while being as small possible to save computational effort. Most available methods systematic are based either on distance single active site or their electrostatic effect. Such approaches might miss non-electrostatic and long-range allosteric interactions. Here, we present proof concept study application protein network analysis tackle this problem. Specifically, explore use centralities descriptor construction. We find that centralities, particular betweenness centrality, can be useful show combination with our previously developed point charge variation analysis, they used identify residues missed purely approaches.

Language: Английский

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Integrated Quantum-Classical Protocol for the Realistic Description of Solvated Multinuclear Mixed-Valence Transition-Metal Complexes and Their Solvatochromic Properties

Journal of Chemical Theory and Computation, Journal Year: 2023, Volume and Issue: 20(3), P. 1306 - 1323

Published: Dec. 12, 2023

Linear cyanide-bridged polymetallic complexes, which undergo photoinduced metal-to-metal charge transfer, represent prototypical systems for studying long-range electron-transfer reactions and understanding the role played by specific solute–solvent interactions in modulating excited-state dynamics. To tackle this problem, while achieving a statistically meaningful description of solvent its relaxation, one needs computational approach capable handling large polynuclear transition-metal both their ground excited states, as well ability to follow dynamics several environments up nanosecond time scales. Here, we present mixed quantum classical approach, combines large-scale molecular (MD) simulations based on an accurate mechanically derived force field (QMD-FF) self-consistent QMD polarized point charges, with IR UV–vis spectral calculations model solvation optical properties cyano-bridged trinuclear mixed-valence compound (trans-[(NC)5FeIII(μ-CN)RuII(pyridine)4(μ-NC)FeIII(CN)5]4–). We demonstrate reliability QMD-FF/MD sampling solute conformational space capturing local comparing results higher-level mechanics/molecular mechanics (QM/MM) MD reference data. The spectra calculated along trajectories different solvents correctly predict red shift CN stretching band aprotic medium (acetonitrile) subtle differences measured water methanol, respectively. By explicitly including molecules around cyanide ligands calculating thermal averaged absorption using time-dependent density functional theory within Tamm–Dancoff approximation, experimental solvatochromic is quantitatively reproduced going from it overestimated acetonitrile. This discrepancy can likely be traced back lack important dispersion between cyano groups pyridine substituents our micro model. proposed protocol applied state water, acetonitrile flexibly generalized study nonequilibrium

Language: Английский

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