Vinícius Wilian D. Cruzeiro

All Publications

• TeraChem protocol buffers (TCPB): Accelerating QM and QM/MM simulations with a client–server model THE JOURNAL OF CHEMICAL PHYSICS Cruzeiro, V. D., Wang, Y., Pieri, E., Hohenstein, E. G., Martínez, T. J. 2023; 158 (044801)

  View details for DOI 10.1063/5.0130886

• Uptake of N2O5 by aqueous aerosol unveiled using chemically accurate many-body potentials NATURE COMMUNICATIONS Cruzeiro, V. D., Galib, M., Limmer, D. T., Gotz, A. W. 2022; 13 (1): 1266

  Abstract

  The reactive uptake of N2O5 to aqueous aerosol is a major loss channel for nitrogen oxides in the troposphere. Despite its importance, a quantitative picture of the uptake mechanism is missing. Here we use molecular dynamics simulations with a data-driven many-body model of coupled-cluster accuracy to quantify thermodynamics and kinetics of solvation and adsorption of N2O5 in water. The free energy profile highlights that N2O5 is selectively adsorbed to the liquid-vapor interface and weakly solvated. Accommodation into bulk water occurs slowly, competing with evaporation upon adsorption from gas phase. Leveraging the quantitative accuracy of the model, we parameterize and solve a reaction-diffusion equation to determine hydrolysis rates consistent with experimental observations. We find a short reaction-diffusion length, indicating that the uptake is dominated by interfacial features. The parameters deduced here, including solubility, accommodation coefficient, and hydrolysis rate, afford a foundation for which to consider the reactive loss of N2O5 in more complex solutions.

  View details for DOI 10.1038/s41467-022-28697-8

  View details for Web of Science ID 000767467900017

  View details for PubMedID 35273144

  View details for PubMedCentralID PMC8913772

• Data for molecular dynamics simulations of Escherichia coli cytochrome bd oxidase with the Amber force field DATA IN BRIEF Ahn, S., Seitz, C., Cruzeiro, D., McCammon, J., Gotz, W. 2021; 38: 107401

  Abstract

  Cytochrome bd-type quinol oxidase is an important metalloenzyme that allows many bacteria to survive in low oxygen conditions. Since bd oxidase is found in many prokaryotes but not in eukaryotes, it has emerged as a promising bacterial drug target. Examples of organisms containing bd oxidases include the Mycobacterium tuberculosis (Mtb) bacterium that causes tuberculosis (TB) in humans, the Vibrio cholerae bacterium that causes cholera, the Pseudomonas aeruginosa bacterium that contributes to antibiotic resistance and sepsis, and the Campylobacter jejuni bacterium that causes food poisoning. Escherichia coli (E. coli) is another organism exhibiting the cytochrome bd oxidase. Since it has the highest sequence identity to Mtb (36%) and we are ultimately interested in finding drug targets for TB, we have built parameters for the E. coli bd oxidase (Protein Data Bank ID number: 6RKO) that are compatible with the all-atom Amber ff14SB force field for molecular dynamics (MD) simulations. Specifically, we built parameters for the three heme cofactors present in all species of bacterial cytochrome bd-type oxidases (heme b 558 , heme b 595 , and heme d) along with their axial ligands. This data report includes the parameter and library files that can be used with Amber's LEaP program to generate input files for MD simulations using the Amber software package. We also provide the PDB data files of the initial model both by itself and solvated with TIP3P water molecules and counterions.

  View details for DOI 10.1016/j.dib.2021.107401

  View details for Web of Science ID 000702923300023

  View details for PubMedID 34621930

  View details for PubMedCentralID PMC8481974

• Harnessing the Power of Multi-GPU Acceleration into the Quantum Interaction Computational Kernel Program JOURNAL OF CHEMICAL THEORY AND COMPUTATION Manathunga, M., Jin, C., Cruzeiro, V. D., Miao, Y., Mu, D., Arumugam, K., Keipert, K., Aktulga, H., Merz, K. M., Goetz, A. W. 2021; 17 (7): 3955-3966

  Abstract

  We report a new multi-GPU capable ab initio Hartree-Fock/density functional theory implementation integrated into the open source QUantum Interaction Computational Kernel (QUICK) program. Details on the load balancing algorithms for electron repulsion integrals and exchange correlation quadrature across multiple GPUs are described. Benchmarking studies carried out on up to four GPU nodes, each containing four NVIDIA V100-SXM2 type GPUs demonstrate that our implementation is capable of achieving excellent load balancing and high parallel efficiency. For representative medium to large size protein/organic molecular systems, the observed parallel efficiencies remained above 82% for the Kohn-Sham matrix formation and above 90% for nuclear gradient calculations. The accelerations on NVIDIA A100, P100, and K80 platforms also have realized parallel efficiencies higher than 68% in all tested cases, paving the way for large-scale ab initio electronic structure calculations with QUICK.

  View details for DOI 10.1021/acs.jctc.1c00145

  View details for Web of Science ID 000674289800013

  View details for PubMedID 34062061

• Highly Accurate Many-Body Potentials for Simulations of N2O5 in Water: Benchmarks, Development, and Validation JOURNAL OF CHEMICAL THEORY AND COMPUTATION Cruzeiro, V. D., Lambros, E., Riera, M., Roy, R., Paesani, F., Gotz, A. W. 2021; 17 (7): 3931-3945

  Abstract

  Dinitrogen pentoxide (N2O5) is an important intermediate in the atmospheric chemistry of nitrogen oxides. Although there has been much research, the processes that govern the physical interactions between N2O5 and water are still not fully understood at a molecular level. Gaining a quantitative insight from computer simulations requires going beyond the accuracy of classical force fields while accessing length scales and time scales that are out of reach for high-level quantum-chemical approaches. To this end, we present the development of MB-nrg many-body potential energy functions for nonreactive simulations of N2O5 in water. This MB-nrg model is based on electronic structure calculations at the coupled cluster level of theory and is compatible with the successful MB-pol model for water. It provides a physically correct description of long-range many-body interactions in combination with an explicit representation of up to three-body short-range interactions in terms of multidimensional permutationally invariant polynomials. In order to further investigate the importance of the underlying interactions in the model, a TTM-nrg model was also devised. TTM-nrg is a more simplistic representation that contains only two-body short-range interactions represented through Born-Mayer functions. In this work, an active learning approach was employed to efficiently build representative training sets of monomer, dimer, and trimer structures, and benchmarks are presented to determine the accuracy of our new models in comparison to a range of density functional theory methods. By assessing the binding curves, distortion energies of N2O5, and interaction energies in clusters of N2O5 and water, we evaluate the importance of two-body and three-body short-range potentials. The results demonstrate that our MB-nrg model has high accuracy with respect to the coupled cluster reference, outperforms current density functional theory models, and thus enables highly accurate simulations of N2O5 in aqueous environments.

  View details for DOI 10.1021/acs.jctc.1c00069

  View details for Web of Science ID 000674289800011

  View details for PubMedID 34029079

• Open-Source Multi-GPU-Accelerated QM/MM Simulations with AMBER and QUICK JOURNAL OF CHEMICAL INFORMATION AND MODELING Cruzeiro, V. D., Manathunga, M., Merz, K. M., Gotz, A. W. 2021; 61 (5): 2109-2115

  Abstract

  The quantum mechanics/molecular mechanics (QM/MM) approach is an essential and well-established tool in computational chemistry that has been widely applied in a myriad of biomolecular problems in the literature. In this publication, we report the integration of the QUantum Interaction Computational Kernel (QUICK) program as an engine to perform electronic structure calculations in QM/MM simulations with AMBER. This integration is available through either a file-based interface (FBI) or an application programming interface (API). Since QUICK is an open-source GPU-accelerated code with multi-GPU parallelization, users can take advantage of "free of charge" GPU-acceleration in their QM/MM simulations. In this work, we discuss implementation details and give usage examples. We also investigate energy conservation in typical QM/MM simulations performed at the microcanonical ensemble. Finally, benchmark results for two representative systems in bulk water, the N-methylacetamide (NMA) molecule and the photoactive yellow protein (PYP), show the performance of QM/MM simulations with QUICK and AMBER using a varying number of CPU cores and GPUs. Our results highlight the acceleration obtained from a single or multiple GPUs; we observed speedups of up to 53× between a single GPU vs a single CPU core and of up to 2.6× when comparing four GPUs to a single GPU. Results also reveal speedups of up to 3.5× when the API is used instead of FBI.

  View details for DOI 10.1021/acs.jcim.1c00169

  View details for Web of Science ID 000656118800001

  View details for PubMedID 33913331

• Relationship between Hydrogen-Bonding Motifs and the 1b(1) Splitting in the X-ray Emission Spectrum of Liquid Water JOURNAL OF PHYSICAL CHEMISTRY LETTERS Cruzeiro, V. D., Wildman, A., Li, X., Paesani, F. 2021; 12 (16): 3996-4002

  Abstract

  The split of the 1b1 peak observed in the X-ray emission (XE) spectrum of liquid water has been the focus of intense research. Although several hypotheses have been proposed to explain the origin of this split, a consensus has not yet been reached. Here, we introduce a novel theoretical/computation approach which, combining path-integral molecular dynamics simulations with the MB-pol model and time-dependent density functional theory calculations, predicts the 1b1 splitting in liquid water and not in crystalline ice, in agreement with the experimental observations. A systematic analysis of the underlying local structure of liquid water at ambient conditions indicates that several different hydrogen-bonding motifs contribute to the overall XE line shape in the energy range corresponding to emissions from the 1b1 orbitals. This suggests that it is not possible to unambiguously attribute the split of the 1b1 peak to only two specific structural arrangements of the underlying hydrogen-bonding network.

  View details for DOI 10.1021/acs.jpclett.1c00486

  View details for Web of Science ID 000647271500018

  View details for PubMedID 33877847

• The density-of-States and equilibrium charge dynamics of redox-active switches Electrochimica Acta Bueno, P. R., Cruzeiro, V. D., Roitberg, A. E., Feliciano, G. T. 2021; 387: 138410

  View details for DOI 10.1016/j.electacta.2021.138410

• Exploring Coupled Redox and pH Processes with a Force-Field-Based Approach: Applications to Five Different Systems JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Cruzeiro, V. D., Feliciano, G., Roitberg, A. E. 2020; 142 (8): 3823-3835

  Abstract

  Coupled redox and pH-driven processes are at the core of many important biological mechanisms. As the distribution of protonation and redox states in a system is associated with the pH and redox potential of the solution, having efficient computational tools that can simulate under these conditions becomes very important. Such tools have the potential to provide information that complement and drive experiments. In previous publications we have presented the implementation of the constant pH and redox potential molecular dynamics (C(pH,E)MD) method in AMBER and we have shown how multidimensional replica exchange can be used to significantly enhance the convergence efficiency of our simulations. In the current work, after an improvement in our C(pH,E)MD approach that allows a given residue to be simultaneously pH- and redox-active, we have employed our methodologies to study five different systems of interest in the literature. We present results for capped tyrosine dipeptide, two maquette systems containing one pH- and redox-active tyrosine (α3Y and peptide A), and two proteins that contain multiple heme groups (diheme cytochrome c from Rhodobacter sphaeroides and Desulfovibrio vulgaris Hildenborough cytochrome c3). We show that our results can provide new insights into previous theoretical and experimental findings by using a fully force-field-based and GPU-accelerated approach, which allows the simulations to be executed with high computational performance.

  View details for DOI 10.1021/jacs.9b11433

  View details for Web of Science ID 000517360400021

  View details for PubMedID 32011132

• Implementing New Educational Platforms in the Classroom: An Interactive Approach to the Particle in a Box Problem JOURNAL OF CHEMICAL EDUCATION Cruzeiro, V. D., Gao, X., Kleiman, V. D. 2019; 96 (8): 1663-1670

  View details for DOI 10.1021/acs.jchemed.9b00195

  View details for Web of Science ID 000516675400015

• Multidimensional Replica Exchange Simulations for Efficient Constant pH and Redox Potential Molecular Dynamics JOURNAL OF CHEMICAL THEORY AND COMPUTATION Cruzeiro, V. D., Roitberg, A. E. 2019; 15 (2): 871-881

  Abstract

  Efficient computational methods that are capable of supporting experimental measures obtained at constant values of pH and redox potential are important tools as they serve to, among other things, provide additional atomic level information that cannot be obtained experimentally. Replica Exchange is an enhanced sampling technique that allows converged results to be obtained faster in comparison to regular molecular dynamics simulations. In this work we report the implementation, also available with GPU-accelerated code, of pH and redox potential (E) as options for multidimensional REMD simulations in AMBER. Previous publications have only reported multidimensional REMD simulations with the temperature and Hamiltonian dimensions. In this work results are shown for N-acetylmicroperoxidase-8 (NAcMP8) axially attached to a histidine peptide. This is a small system that contains only a single heme group. We compare results from E,pH-REMD, E,T-REMD, and E,T,pH-REMD to one-dimensional REMD simulations and to simulations without REMD. We show that two-dimensional REMD simulations improve sampling convergence in comparison to one-dimensional REMD simulations and that three-dimensional REMD further improves convergence in comparison to two-dimensional REMD simulations. Also, our computational benchmarks show that our multidimensional REMD calculations have a small and bearable computational performance, essentially the same as one-dimensional REMD. However, multidimensional REMD makes use of a significantly higher number of replicas because the number of replicas scales geometrically with the number of dimensions; therefore, more computational resources are required. In addition to the pH dependence on standard redox potential values and the redox potential dependence on p Ka values, we also investigate the influence of the temperature in our results. We observe an agreement between our computational results and purely theoretical predictions.

  View details for DOI 10.1021/acs.jctc.8b00935

  View details for Web of Science ID 000458937600006

  View details for PubMedID 30615455

• Probing the Structures of Solvent-Complexed Ions Formed in Electrospray Ionization Using Cryogenic Infrared Photodissociation Spectroscopy JOURNAL OF PHYSICAL CHEMISTRY A Bell, M. R., Cruzeiro, V. D., Cismesia, A. P., Tesler, L. F., Roitberg, A. E., Polfer, N. C. 2018; 122 (37): 7427-7436

  Abstract

  The gas-phase infrared photodissociation (IRPD) spectra of solvent-tagged small biomolecules are studied in a cryogenic ion trap at 17 K. In this study para-aminobenzoic acid (PABA) and tyramine molecules are noncovalently tagged with water or acetonitrile in the electrospray ionization (ESI) source. The complexes are then cooled in the cryogenic trap prior to spectroscopic measurements. These molecules provide two putative sites for solvent attachment: the protonated amine (NH3+) and the OH groups. Comparisons of the experimental IR spectra to theoretical spectra obtained with density functional theory show that the NH3+ site is mainly favored. Evidence for the formation of both NH3-bound and OH-bound conformers is found only in tyramine, despite having similar solution- and gas-phase energetics to that of PABA. Since the structures cannot interconvert in the gas phase, this suggests an isomerization during the electrospray process.

  View details for DOI 10.1021/acs.jpca.8b05896

  View details for Web of Science ID 000445711900019

  View details for PubMedID 30126276

• Cation-dependent conformations in 25-hydroxyvitamin D3-cation adducts measured by ion mobility-mass spectrometry and theoretical modeling INTERNATIONAL JOURNAL OF MASS SPECTROMETRY Chouinard, C. D., Cruzeiro, V. D., Kemperman, R. J., Oranzi, N. R., Roitberg, A. E., Yost, R. A. 2018; 432: 1-8

  Abstract

  Ion mobility-mass spectrometry is a useful tool in separation of biological isomers, including clinically relevant analytes such as 25-hydroxyvitamin D3 (25OHD3) and its epimer, 3-epi-25-hydroxyvitamin D3 (epi25OHD3). Previous research indicates that these epimers adopt different gas-phase sodiated monomer structures, either the "open" or "closed" conformer, which allow 25OHD3 to be readily resolved in mixtures. In the current work, alternative metal cation adducts are investigated for their relative effects on the ratio of "open" and "closed conformers. Alkali and alkaline earth metal adducts caused changes in the 25OHD3 conformer ratio, where the proportion of the "open" conformer generally increases with the size of the metal cation in a given group. As such, the ratio of the "open" conformer, which is unique to 25OHD3 and absent for its epimer, can be increased from approximately 1:1 for the sodiated monomer to greater than 8:1 for the barium adduct. Molecular modeling and energy calculations agree with the experimental results, indicating that the Gibbs free energy of conversion from the "closed" to the "open" conformation decreased with increasing cation size, correlating with the variation in ratio between the conformers. This work demonstrates the effect of cation adducts on gas-phase conformations of small, flexible molecules and offers an additional strategy for resolution of clinically relevant epimers.

  View details for DOI 10.1016/j.ijms.2018.05.013

  View details for Web of Science ID 000444626800001

  View details for PubMedID 30034270

  View details for PubMedCentralID PMC6052799

• Redox potential replica exchange molecular dynamics at constant pH in AMBER: implementation and validation JOURNAL OF CHEMICAL PHYSICS Cruzeiro, V. D., Amaral, M. S., Roitberg, A. E. 2018; 149 (7): 072338

  Abstract

  Redox processes are important in chemistry, with applications in biomedicine, chemical analysis, among others. As many redox experiments are also performed at a fixed value of pH, having an efficient computational method to support experimental measures at both constant redox potential and pH is very important. Such computational techniques have the potential to validate experimental observations performed under these conditions and to provide additional information unachievable experimentally such as an atomic level description of macroscopic measures. We present the implementation of discrete redox and protonation states methods for constant redox potential Molecular Dynamics (CEMD), for coupled constant pH and constant redox potential MD (C(pH,E)MD), and for Replica Exchange MD along the redox potential dimension (E-REMD) on the AMBER software package. Validation results are presented for a small system that contains a single heme group: N-acetylmicroperoxidase-8 (NAcMP8) axially connected to a histidine peptide. The methods implemented allow one to make standard redox potential (Eo) predictions with the same easiness and accuracy as pKa predictions using the constant pH molecular dynamics and pH-REMD methods currently available on AMBER. In our simulations, we can correctly describe, in agreement also with theoretical predictions, the following behaviors: when a redox-active group is reduced, the pKa of a near pH-active group increases because it becomes easier for a proton to be attached; equivalently, when a pH-active group is protonated, the standard redox potential (Eo) of an adjacent redox-active group rises. Furthermore, our results also show that E-REMD is able to achieve faster statistical convergence than CEMD or C(pH,E)MD. Moreover, computational benchmarks using our methodologies show high-performance of GPU (Graphics Processing Unit) accelerated calculations in comparison to conventional CPU (Central Processing Unit) calculations.

  View details for DOI 10.1063/1.5027379

  View details for Web of Science ID 000442425200039

  View details for PubMedID 30134669

• Investigating Differences in Gas-Phase Conformations of 25-Hydroxyvitamin D3 Sodiated Epimers using Ion Mobility-Mass Spectrometry and Theoretical Modeling JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY Chouinard, C. D., Cruzeiro, V. D., Beekman, C. R., Roitberg, A. E., Yost, R. A. 2017; 28 (8): 1497-1505

  Abstract

  Drift tube ion mobility coupled with mass spectrometry was used to investigate the gas-phase structure of 25-hydroxyvitamin D3 (25OHD3) and D2 (25OHD2) epimers, and to evaluate its potential in rapid separation of these compounds. Experimental results revealed two distinct drift species for the 25OHD3 sodiated monomer, whereas only one of these conformations was observed for its epimer (epi25OHD3). The unique species allowed 25OHD3 to be readily distinguished, and the same pattern was observed for 25OHD2 epimers. Theoretical modeling of 25OHD3 epimers identified energetically stable gas-phase structures, indicating that both compounds may adopt a compact "closed" conformation, but that 25OHD3 may also adopt a slightly less energetically favorable "open" conformation that is not accessible to its epimer. Calculated theoretical collision cross-sections for these structures agreed with experimental results to <2%. Experimentation indicated that additional energy in the ESI source (i.e., increased temperature, spray voltage) affected the ratio of 25OHD3 conformations, with the less energetically favorable "open" conformation increasing in relative intensity. Finally, LC-IM-MS results yielded linear quantitation of 25OHD3, in the presence of the epimer interference, at biologically relevant concentrations. This study demonstrates that ion mobility can be used in tandem with theoretical modeling to determine structural differences that contribute to drift separation. These separation capabilities provide potential for rapid (<60 ms) identification of 25OHD3 and 25OHD2 in mixtures with their epimers. Graphical Abstract ᅟ.

  View details for DOI 10.1007/s13361-017-1673-4

  View details for Web of Science ID 000405486200002

  View details for PubMedID 28417307

• Experimental and Theoretical Investigation of Sodiated Multimers of Steroid Epimers with Ion Mobility-Mass Spectrometry JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY Chouinard, C. D., Cruzeiro, V. D., Roitberg, A. E., Yost, R. A. 2017; 28 (2): 323-331

  Abstract

  Ion mobility-mass spectrometry (IM-MS) has recently seen increased use in the analysis of small molecules, especially in the field of metabolomics, for increased breadth of information and improved separation of isomers. In this study, steroid epimers androsterone and trans-androsterone were analyzed with IM-MS to investigate differences in their relative mobilities. Although sodiated monomers exhibited very similar collision cross-sections (CCS), baseline separation was observed for the sodiated dimer species (RS = 1.81), with measured CCS of 242.6 and 256.3 Å2, respectively. Theoretical modeling was performed to determine the most energetically stable structures of solution-phase and gas-phase monomer and dimer structures. It was revealed that these epimers differ in their preferred dimer binding mode in solution phase: androsterone adopts a R=O - Na+ - OH-R' configuration, whereas trans-androsterone adopts a R=O - Na+ - O=R' configuration. This difference contributes to a significant structural variation, and subsequent CCS calculations based on these structures relaxed in the gas phase were in agreement with experimentally measured values (ΔCCS ~ 5%). Additionally, these calculations accurately predicted the relative difference in mobility between the epimers. This study illustrates the power of combining experimental and theoretical results to better elucidate gas-phase structures. Graphical Abstract ᅟ.

  View details for DOI 10.1007/s13361-016-1525-7

  View details for Web of Science ID 000392319600014

  View details for PubMedID 27914014

  View details for PubMedCentralID PMC5478531

• Structure-Activity Relationships of Benzenesulfonamide-Based Inhibitors towards Carbonic Anhydrase Isoform Specificity CHEMBIOCHEM Bhatt, A., Mahon, B. P., Cruzeiro, V. D., Cornelio, B., Laronze-Cochard, M., Ceruso, M., Sapi, J., Rance, G. A., Khlobystov, A. N., Fontana, A., Roitberg, A., Supuran, C. T., McKenna, R. 2017; 18 (2): 213-222

  Abstract

  Carbonic anhydrases (CAs) are implicated in a wide range of diseases, including the upregulation of isoforms CA IX and XII in many aggressive cancers. However, effective inhibition of disease-implicated CAs should minimally affect the ubiquitously expressed isoforms, including CA I and II, to improve directed distribution of the inhibitors to the cancer-associated isoforms and reduce side effects. Four benzenesulfonamide-based inhibitors were synthesized by using the tail approach and displayed nanomolar affinities for several CA isoforms. The crystal structures of the inhibitors bound to a CA IX mimic and CA II are presented. Further in silico modeling was performed with the inhibitors docked into CA I and XII to identify residues that contributed to or hindered their binding interactions. These structural studies demonstrated that active-site residues lining the hydrophobic pocket, especially positions 92 and 131, dictate the positional binding and affinity of inhibitors, whereas the tail groups modulate CA isoform specificity. Geometry optimizations were performed on each ligand in the crystal structures and showed that the energetic penalties of the inhibitor conformations were negligible compared to the gains from active-site interactions. These studies further our understanding of obtaining isoform specificity when designing small molecule CA inhibitors.

  View details for DOI 10.1002/cbic.201600513

  View details for Web of Science ID 000392936800011

  View details for PubMedID 27860128

• Interactively Applying the Variational Method to the Dihydrogen Molecule: Exploring Bonding and Antibonding JOURNAL OF CHEMICAL EDUCATION Cruzeiro, V. D., Roitberg, A., Polfer, N. C. 2016; 93 (9): 1578-1585

  View details for DOI 10.1021/acs.jchemed.6b00017

  View details for Web of Science ID 000383828700013

• Free base phthalocyanine: Influence of thermal effects and dimerization on the electronic absorption spectrum CHEMICAL PHYSICS LETTERS Cabral, B. C., Cruzeiro, V. D., Coutinho, K., Canuto, S. 2014; 595: 97-102

  View details for DOI 10.1016/j.cplett.2014.01.047

  View details for Web of Science ID 000332957100018