arXiv subjects
Publications and source records attributed to Daniel Mejia-Rodriguez.
A thermodynamic integration (TI) protocol incorporating dummy atoms is introduced to calculate free energy differences for disulfide bond formation in proteins. This method successfully reproduces experimental redox potentials for multiple proteins, providing improved insights into the redox regulation of various proteins.
Cyanobacteria require ultra-fast metabolic switching to maintain reducing power balance during environmental fluctuations. Glucose-6-phosphate dehydrogenase (G6PDH), catalyzing the rate-limiting step of the oxidative pentose phosphate pathway (OPPP), provides essential NADPH and metabolic intermediates for biosynthetic processes and redox homeostasis. In cyanobacteria, the unique redox-sensitive protein OpcA acts as a metabolic switch for G6PDH, enabling rapid adjustment of reducing power generation from glycogen catabolism and resulting in precise regulation of carbon flux between anabolic and catabolic pathways. While the redox-sensitive cysteine structures of OpcA are known to regulate G6PDH, the detailed mechanisms of how redox post-translational modifications (PTMs) influence OpcA's allosteric effects on G6PDH structures and function remain elusive. To investigate this mechanism, we utilized computational modeling combined with experimental redox proteomics using Synechococcus elongatus PCC 7942 as a model system. Redox proteomics captured modified cysteine residues under light/dark or circadian shifts. Computational simulation revealed that thiol PTMs near the OpcA-G6PDH interface are crucial to allosteric regulation of regions affecting the G6PDH activity, including a potential gate region for substrate ingress and product egress, as well as critical hydrogen bond networks within the active site. These PTMs promote rapid metabolic switching by enhancing G6PDH catalytic activity when OpcA is oxidized. This study provides evidence for novel molecular mechanisms that elucidate the importance of thiol PTMs of OpcA in modulating G6PDH structure and function in an allosteric manner, demonstrating how PTM-level regulation provides a critical control mechanism that enables cyanobacteria to rapidly adapt to environmental fluctuations through precise metabolic fine-tuning.
We developed an advanced computational framework to accelerate the study of the impact of post-translational modifications on protein structures and interactions (PTM-Psi) using asynchronous, loosely coupled workflows on the Azure Quantum Elements Cloud platform. We seamlessly integrate emerging cloud computing assets that further expand the scope and capability of PTM-Psi Python package by refactoring it into a cloud-compatible library. We employed a "workflow of workflows" approach wherein a parent workflow spawns one or more child workflows, managing them, and acting on their results. This approach enabled us to optimize resource allocation according to each workflow's needs, and allowed us to use the cloud heterogeneous architecture for the computational investigation of a combinatorial explosion of thiol protein PTMs on an exemplary protein megacomplex critical to the Calvin-Benson cycle of light-dependent sugar production in cyanobacteria. With PTM-Psi on the cloud, we transformed the pipeline for the thiol PTM analysis to achieve high throughput by leveraging the strengths of the cloud service. \ptmpsi\ on the cloud reduces operational complexity and lowers entry barriers to data interpretation with structural modeling for a redox proteomics mass spectrometry specialist.
The intersection of quantum computing and quantum chemistry represents a promising frontier for achieving quantum utility in domains of both scientific and societal relevance. Owing to the exponential growth of classical resource requirements for simulating quantum systems, quantum chemistry has long been recognized as a natural candidate for quantum computation. This perspective focuses on identifying scientifically meaningful use cases where early fault-tolerant quantum computers, which are considered to be equipped with approximately 25--100 logical qubits, could deliver tangible impact. While recent advances in classical computing have pushed the boundaries of tractable simulations to unprecedented scales, this logical-qubit regime represents the first window where quantum devices can pursue qualitatively distinct strategies, such as polynomial-scaling phase estimation, direct simulation of quantum dynamics, and active-space embedding, that remain challenging for classical solvers, for instance, multireference charge-transfer and conical-intersection states central to photochemistry and materials design. We highlight near-term opportunities in algorithm and software design, discuss representative chemical problems suited for quantum acceleration, and propose strategic roadmaps and collaborative pathways for advancing practical quantum utility in quantum chemistry.
The $GW$ approximation has become an important tool for predicting charged excitations of isolated molecules and condensed systems. Its popularity can be attributed to many factors, including a favorable scaling and relatively good accuracy. In practical applications, the $GW$ is often performed as a one-shot perturbation known as $G_0W_0$. Unfortunately, $G_0W_0$ suffers from a strong starting point dependence and is often not as accurate as one would need. Self-consistent $GW$ methodologies alleviate these problems but come with a marked increase in computational cost. In this manuscript, we propose the use of an estimate of the exchange-correlation derivative discontinuity to provide a remarkably good starting point for $G_0W_0$ calculations, yielding ionization potentials and electron affinities with eigenvalue self-consistent $GW$ quality at no additional cost. We assess the quality of the resulting methodology with the GW100 benchmark set and compare its advantages over other similar methods.
We report computations of the vertical ionization potentials within the $GW$ approximation of the near-complete series of first-row transition metal (V-Cu) aqua ions in their most common oxidation states, i.e. V$^{3+}$, Cr$^{3+}$, Cr$^{2+}$, Mn$^{2+}$, Fe$^{3+}$, Fe$^{2+}$, Co$^{2+}$, Ni$^{2+}$, and Cu$^{2+}$. The $d$-orbital occupancy of these systems spans a broad range from $d^2$ to $d^9$. All the structures were first optimized at the density functional theory level using a large cluster of explicit water molecules that are embedded in a continuum solvation model. Vertical ionization potentials were computed with the one-shot $G_0W_0$ approach on a range of transition metal ion clusters (6, 18, 40, and 60 explicit water molecules) wherein the convergence with respect to the basis set size was evaluated using the systems with 40 water molecules. We assess the results using three different density functional approximations as starting points for the vertical ionization potential calculations, namely $G_0W_0$@PBE, $G_0W_0$@PBE0, and $G_0W_0$@r$^2$SCAN. While the predicted ground-state structures are similar with all three exchange-correlation functionals, the vertical ionization potentials were in closer agreement with the experiment when using the $G_0W_0$@PBE0 and $G_0W_0$@r$^2$SCAN approaches, with the r2SCAN based calculations being significantly less expensive. Computed bond distances and vertical ionization potentials for all structures were compared with available experimental data and are in good agreement.
The $GW$ approximation has been recently gaining popularity among the method for simulating molecular core-level X-ray photoemission spectra. Traditionally, $GW$ core-level binding energies have been computed using either the cc-pV$n$Z or def2-$n$ZVP basis set families, extrapolating the obtained results to the complete basis set limit, followed by a an element-specific relativistic correction. Despite of achieving good accuracy, these binding energies are chronically underestimated. By using first-row elements and standard techniques known to offer good cost-accuracy ratio in other theories, we show that the cc-pV$n$Z and def2-$n$ZVP families show large contraction errors and lead to unreliable complete basis set extrapolations. On the other hand, we demonstrate that uncontracted versions of these basis sets offer vastly improved convergence. Even faster convergence can be obtained using core-rich, property-optimized, basis sets families like pcSseg-$n$, pcJ-$n$ and ccX-$n$Z. Finally, we also show that the improvement over the core properties does not degrade the calculation of the valence excitations, and thus offer a balanced description of both core and valence regions.
We present a scalable implementation of the $GW$ approximation using Gaussian atomic orbitals to study the valence and core ionization spectroscopies of molecules. The implementation of the standard spectral decomposition approach to the screened Coulomb interaction, as well as a contour deformation method are described. We have implemented both of these approaches using the robust variational fitting approximation to the four-center electron repulsion integrals. We have utilized the MINRES solver with the contour deformation approach to reduce the computational scaling by one order of magnitude. A complex heuristic in the quasiparticle equation solver further allows a speed-up of the computation of core and semi-core ionization energies. Benchmark tests using the GW100 and CORE65 datasets and the carbon 1{\it s} binding energy of the well-studied ethyl trifluoroacetate, or ESCA molecule, were performed to validate the accuracy of our implementation. We also demonstrate and discuss the parallel performance and computational scaling of our implementation using a range of water clusters of increasing size.
The recent major modification, r$^2$SCAN, of the SCAN (strongly constrained and appropriately normed) meta-GGA exchange-correlation functional is shown to give substantially better spin-crossover electronic energies (high spin minus low spin) on a benchmark data set than the original SCAN. The deorbitalized counterpart r$^2$SCAN-L is almost as good as SCAN and much faster in periodically bounded systems. A combination strategy for balanced treatment of molecular and periodic spin-crossover therefore is recommended.
A recent modification, r$^2$SCAN, of the SCAN (strongly constrained and appropriately normed) meta-GGA exchange-correlation functional mostly eliminates numerical instabilities and attendant integration grid sensitivities exhibited by SCAN. Here we show that the successful deorbitalization of SCAN to SCAN-L (SCAN with density Laplacian dependence) carries over directly to yield r$^2$SCAN-L. A major benefit is that the high iteration counts that hindered use of SCAN-L are eliminated in r$^2$SCAN-L. It therefore is a computationally much faster meta-GGA than its orbital-dependent antecedent. Validation data for molecular heats of formation, bond lengths, and vibration frequencies (G3/99X, T96-R, T82-F test sets respectively) and on lattice constants, and cohesive energies (for 55 solids) and bulk moduli (for 40 solids) are provided. In addition, we show that the over-magnetization of bcc Fe from SCAN persists in r$^2$SCAN but does not appear in r$^2$SCAN-L, just as with SCAN-L.
Recent investigations have found that the strongly constrained and appropriately normed (SCAN) meta-GGA exchange-correlation functional significantly over-magnetizes elemental Fe, Co, and Ni solids. For the paradigmatic case, bcc Fe, the error relative to experiment is $\gtrsim 20 \%$. Comparative analysis of magnetization results from SCAN and its \textit{deorbitalized} counterpart, SCAN-L, leads to identification of the source of the discrepancy. It is not from the difference between Kohn-Sham (SCAN-L) and generalized Kohn-Sham (SCAN) procedures. The key is the iso-orbital indicator $α$ (the ratio of the local Pauli and Thomas-Fermi kinetic energy densities). Its \textit{deorbitalized} counterpart, $α_L$, has more dispersion in both spin channels with respect to magnetization in an approximate region between 0.6 Bohr and 1.2 Bohr around an Fe nucleus. The overall effect is that the SCAN switching function evaluated with $α_L$ reduces the energetic disadvantage of the down channel with respect to up compared to the original $α$, which in turn reduces the magnetization. This identifies the cause of the SCAN magnetization error as insensitivity of the SCAN switching function to $α$ values in the approximate range $0.5 \lesssim α\lesssim 0.8$ and oversensitivity for $α\gtrsim 0.8$.
A procedure for removing explicit orbital dependence from meta-generalized-gradient approximation (mGGA) exchange-correlation functionals by converting them into Laplacian-dependent functionals recently was developed by us and shown to be successful in molecules. It uses an approximate kinetic energy density functional (KEDF) parametrized to Kohn-Sham results (not experimental data) on a small training set. Here we present extensive validation calculations on periodic solids that demonstrate that the same deorbitalization with the same parametrization also is successful for those extended systems. Because of the number of stringent constraints used in its construction and its recent prominence, our focus is on the SCAN meta-GGA. Coded in \textsc{vasp}, the deorbitalized version, SCAN-L, can be as much as a factor of three faster than original SCAN, a potentially significant gain for large-scale ab initio molecular dynamics.
We explore the simplification of widely used meta-generalized-gradient approximation (mGGA) exchange-correlation functionals to the Laplacian level of refinement by use of approximate kinetic energy density functionals (KEDFs). Such deorbitalization is motivated by the prospect of reducing computational cost while recovering a strictly Kohn-Sham local potential framework (rather than the usual generalized Kohn-Sham treatment of mGGAs). A KEDF that has been rather successful in solid simulations proves to be inadequate for deorbitalization but we produce other forms which, with parametrization to Kohn-Sham results (not experimental data) on a small training set, yield rather good results on standard molecular test sets when used to deorbitalize the meta-GGA made very simple, TPSS, and SCAN functionals. We also study the difference between high-fidelity and best-performing deorbitalizations and discuss possible implications for use in ab initio molecular dynamics simulations of complicated condensed phase systems.