Recent developments in QM/MM for Molecular Dynamics

Question

I am looking for new QM/MM methodologies which have recently developed and implemented into MD packages. Any applications or molecular systems studies with these methods can be used as an example as well.

Answer 1

Machine Learning

There are several examples about how Machine Learning is been used in Quantum Chemistry. Here I bring two of them that are directly related with QM/MM calculations.

• L. Böselt, M. Thürlemann, and S. Riniker. Machine Learning in QM/MM Molecular Dynamics Simulations of Condensed-Phase Systems, (2021) DOI: 10.1021/acs.jctc.0c01112, PDF. Abstract: Quantum mechanics/molecular mechanics (QM/MM) molecular dynamics (MD) simulations have been developed to simulate molecular systems, where an explicit description of changes in the electronic structure is necessary. However, QM/MM MD simulations are computationally expensive compared to fully classical simulations as all valence electrons are treated explicitly and a self-consistent field (SCF) procedure is required. Recently, approaches have been proposed to replace the QM description with machine-learned (ML) models. However, condensed-phase systems pose a challenge for these approaches due to long-range interactions. Here, we establish a workflow, which incorporates the MM environment as an element type in a high-dimensional neural network potential (HDNNP). The fitted HDNNP describes the potential-energy surface of the QM particles with an electrostatic embedding scheme. Thus, the MM particles feel a force from the polarized QM particles. To achieve chemical accuracy, we find that even simple systems require models with a strong gradient regularization, a large number of data points, and a substantial number of parameters. To address this issue, we extend our approach to a Δ-learning scheme, where the ML model learns the difference between a reference method (density functional theory (DFT)) and a cheaper semiempirical method (density functional tight binding (DFTB)). We show that such a scheme reaches the accuracy of the DFT reference method while requiring significantly less parameters. Furthermore, the Δ-learning scheme is capable of correctly incorporating long-range interactions within a cutoff of 1.4 nm. It is validated by performing MD simulations of retinoic acid in water and the interaction between S-adenoslymethioniat and cytosine in water. The presented results indicate that Δ-learning is a promising approach for (QM)ML/MM MD simulations of condensed-phase systems.
• T. Morawietz, N. Artrith, Machine learning-accelerated quantum mechanics-based atomistic simulations for industrial applications. J Comput Aided Mol Des 35, 557–586 (2021). DOI: 10.1007/s10822-020-00346-6. PDF. Abstract: Atomistic simulations have become an invaluable tool for industrial applications ranging from the optimization of protein-ligand interactions for drug discovery to the design of new materials for energy applications. Here we review recent advances in the use of machine learning (ML) methods for accelerated simulations based on a quantum mechanical (QM) description of the system. We show how recent progress in ML methods has dramatically extended the applicability range of conventional QM-based simulations, allowing to calculate industrially relevant properties with enhanced accuracy, at reduced computational cost, and for length and time scales that would have otherwise not been accessible. We illustrate the benefits of ML-accelerated atomistic simulations for industrial R&D processes by showcasing relevant applications from two very different areas, drug discovery (pharmaceuticals) and energy materials. Writing from the perspective of both a molecular and a materials modeling scientist, this review aims to provide a unified picture of the impact of ML-accelerated atomistic simulations on the pharmaceutical, chemical, and materials industries and gives an outlook on the exciting opportunities that could emerge in the future.