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We develop a new deep potential-range correction (DPRc) machine learning potential for combined quantum mechanical/molecular mechanical (QM/MM) simulations of chemical reactions in the condensed phase. The new range correction enables short-ranged QM/MM interactions to be tuned for higher accuracy, and the correction smoothly vanishes within a specified cutoff. We further develop an active learning procedure for robust neural network training. We test the DPRc model and training procedure against a series of six nonenzymatic phosphoryl transfer reactions in solution that are important in mechanistic studies of RNA- cleaving enzymes. Specifically, we apply DPRc corrections to a base QM model and test its ability to reproduce free-energy profiles generated from a target QM model. We perform these comparisons using the MNDO/d and DFTB2 semiempirical models because they differ in the way they treat orbital orthogonalization and electrostatics and produce free-energy profiles which differ significantly from each other, thereby providing us a rigorous stress test for the DPRc model and training procedure. The comparisons show that accurate reproduction of the free-energy profiles requires correction of the QM/MM interactions out to 6 angstrom. We further find that the model's initial training benefits from generating data from temperature replica exchange simulations and including high-temperature configurations into the fitting procedure, so the resulting models are trained to properly avoid high-energy regions. A single DPRc model was trained to reproduce four different reactions and yielded good agreement with the free-energy profiles made from the target QM/MM simulations. The DPRc model was further demonstrated to be transferable to 2D free-energy surfaces and 1D free-energy profiles that were not explicitly considered in the training. Examination of the computational performance of the DPRc model showed that it was fairly slow when run on CPUs but was sped up almost 100-fold when using NVIDIA V100 GPUs, resulting in almost negligible overhead. The new DPRc model and training procedure provide a potentially powerful new tool for the creation of next-generation QM/MM potentials for a wide spectrum of free-energy applications ranging from drug discovery to enzyme design.

We demonstrate the capability of embedded mean-field theory (EMFT) within the linear-scaling density-functional-theory code ONETEP, which enables DFT-in-DFT quantum embedding calculations on systems containing thousands of atoms at a fraction of the cost of a full calculation. We perform simulations on a wide range of systems from molecules to complex nanostructures to demonstrate the performance of our implementation with respect to accuracy and efficiency. This work paves the way for the application of this class of quantum embedding method to large-scale systems that are beyond the reach of existing implementations.

DNA cyclization is a powerful technique to gain insight into the nature of DNA bending. While the worm-like chain model provides a good description of small to moderate bending fluctuations, it is expected to break down for large bending. Recent cyclization experiments on strongly-bent shorter molecules indeed suggest enhanced flexibility over and above that expected from the worm-like chain. Here, we use a coarse-grained model of DNA to investigate the subtle thermodynamics of DNA cyclization for molecules ranging from 30 to 210 base pairs. As the molecules get shorter we find increasing deviations between our computed equilibrium j-factor and the classic worm-like chain predictions of Shimada and Yamakawa for a torsionally aligned looped molecule. These deviations are due to sharp kinking, first at nicks, and only subsequently in the body of the duplex. At the shortest lengths, substantial fraying at the ends of duplex domains is the dominant method of relaxation. We also estimate the dynamic j-factor measured in recent FRET experiments. We find that the dynamic j-factor is systematically larger than its equilibrium counterpart - with the deviation larger for shorter molecules - because not all the stress present in the fully cyclized state is present in the transition state. These observations are important for the interpretation of recent cyclization experiments, suggesting that measured anomalously high j-factors may not necessarily indicate non-WLC behavior in the body of duplexes.

Geometrical and electronic structures of the chromium oxide dimer in both charge states Cr2O2-/0 were carefully and thoroughly studied using the restricted active space RASSCF/RASPT2 and density matrix renormalization group followed by second-order perturbation theory DMRG-CASPT2 methods in conjunction with large basis sets. The anionic and neutral clusters Cr2O2-/0 are characterized by a D2 h structure and high-spin ground states (10 and 9, respectively). RASSCF wave functions point out strong multireference characters of their electronic ground state. The two lowest-lying states 10Ag and 10B2g of the anion Cr2O2- are nearly degenerate, and both were proven to be populated and involved in the anion photoelectron spectra of Cr2O2-. The neutral cluster exhibits a 9B2g ground state. Within the active space of 20 electrons in 18 orbitals used, 30 electronic transitions starting from both lower-lying anionic states to corresponding neutral states were predicted. Transitions from the anionic ground state 10Ag cause most of visible bands in the anion photoelectron spectra of Cr2O2-, while the first band with low intensity is determined to arise from a transition starting from the nearly degenerate state 10B2g. Furthermore, multidimensional Franck-Condon factor simulations were carried out to further support our band assignments. ispartof: JOURNAL OF CHEMICAL THEORY AND COMPUTATION vol:14 issue:9 pages:4833-4843 ispartof: location:United States status: published

In previous work on the performance of multiconfigurational second-order perturbation theory (CASPT2) in describing spin state energetics in first-row transition metal systems [ Pierloot et al. J. Chem. Theory Comput. 2017 , 13 , 537 - 553 ], we showed that standard CASPT2 works well for valence correlation but does not describe the metal semicore (3s3p) correlation effects accurately. This failure is partially responsible for the well-known bias toward high-spin states of CASPT2. In this paper, we expand our previous work and show that this bias could be partly removed with a combined CASPT2/CC approach: using high-quality CASPT2 with extensive correlation-consistent basis sets for valence correlation and low-cost CCSD(T) calculations with minimal basis sets for the metal semicore (3s3p) correlation effects. We demonstrate that this approach is efficient by studying the spin state energetics of a series of iron complexes modeling important intermediates in oxidative catalytic processes in chemistry and biochemistry. On the basis of a comparison with bare CCSD(T) results from this and previous work, the average error of the CASPT2/CC approach is estimated at around 2 kcal mol-1 in favor of high spin states. ispartof: JOURNAL OF CHEMICAL THEORY AND COMPUTATION vol:14 issue:5 pages:2446-2455 ispartof: location:United States status: published

We employed our recently proposed multireference approach CASPT2/CC to calculate the quintet-triplet gaps ΔETQ of a series of non-heme FeIV═O species and subsequently used these results to benchmark density functional theory (DFT) as well as two variants of local coupled-cluster approaches (DLPNO-CCSD(T) and LUCCSD(T0)). We showed that current implementations of the local coupled-cluster method are not sufficiently accurate. DLPNO-CCSD(T) systematically overstabilizes the quintet state, whereas LUCCSD(T0) overestimates the triplet one. This sort of systematic bias may be helpful in improving local correlation methods and can also be used as the basis for a simple correction scheme. ispartof: JOURNAL OF CHEMICAL THEORY AND COMPUTATION vol:15 issue:8 pages:4297-4304 ispartof: location:United States status: published

Building on the success of Quantum Monte Carlo techniques such as diffusion Monte Carlo, alternative stochastic approaches to solve electronic structure problems have emerged over the past decade. The full configuration interaction quantum Monte Carlo (FCIQMC) method allows one to systematically approach the exact solution of such problems, for cases where very high accuracy is desired. The introduction of FCIQMC has subsequently led to the development of coupled cluster Monte Carlo (CCMC) and density matrix quantum Monte Carlo (DMQMC), allowing stochastic sampling of the coupled cluster wave function and the exact thermal density matrix, respectively. In this Article, we describe the HANDE-QMC code, an open source implementation of FCIQMC, CCMC and DMQMC, including initiator and semistochastic adaptations. We describe our code and demonstrate its use on three example systems; a molecule (nitric oxide), a model solid (the uniform electron gas), and a real solid (diamond). An illustrative tutorial is also included. Public domain – authored by a U.S. government employee

Current force fields underestimate significantly the dielectric constant of formamide at standard conditions. We present a derivation of an accurate potential for formamide, with a functional form based on the OPLS/AA force field. Our procedure follows the approach introduced by Salas et al. ( J. Chem. Theory Comput. 2015 , 11 , 683 - 693 ) that relies on ab initio calculations and molecular dynamics simulations. We consider several strategies to derive the atomic charges of formamide. We find that the inclusion of polarization effects in the quantum mechanical computations is essential to obtain reliable force fields. By varying the atomic charges and the Lennard-Jones parameters describing the dispersion interactions in the OPLS/AA force field, we derive an optimum set of parameters that provides accurate results for the dielectric constant, surface tension, and bulk density of liquid formamide in a wide range of thermodynamic states. We test the transferability of our parameters to investigate liquid/liquid mixtures. We have chosen as case study an equimolar mixture of formamide and hexan-2-one. This mixture involves two fluids with very different polar characteristics, namely, large differences in their dielectric constants and their performance as solvents. The new potential predicts a liquid/liquid phase separation, in good agreement with experimental data, and highlights the importance of the correct parametrization of the pure liquid phases to investigate liquid mixtures. Finally, we examine the microscopic origin of the observed inmiscibility between formamide and hexa-2-one.