@article{dolgova_yu_cvitkovic_hodak_nienaber_summers_cotelesage_bernholc_kaminski_pickering_et al._2017, title={Binding of Copper and Cisplatin to Atox1 Is Mediated by Glutathione through the Formation of Metal–Sulfur Clusters}, volume={56}, ISSN={0006-2960 1520-4995}, url={http://dx.doi.org/10.1021/acs.biochem.7b00293}, DOI={10.1021/acs.biochem.7b00293}, abstractNote={Copper is an essential nutrient required for many biological processes involved in primary metabolism, but free copper is toxic due to its ability to catalyze formation of free radicals. To prevent toxic effects, in the cell copper is bound to proteins and low molecular weight compounds, such as glutathione, at all times. The widely used chemotherapy agent cisplatin is known to bind to copper-transporting proteins, including copper chaperone Atox1. Cisplatin interactions with Atox1 and other copper transporters are linked to cancer resistance to platinum-based chemotherapy. Here we analyze the binding of copper and cisplatin to Atox1 in the presence of glutathione under redox conditions that mimic intracellular environment. We show that copper(I) and glutathione form large polymers with a molecular mass of approximately 8 kDa, which can transfer copper to Atox1. Cisplatin also can form polymers with glutathione, albeit at a slower rate. Analysis of simultaneous binding of copper and cisplatin to Atox1 under physiological conditions shows that both metals are bound to the protein through copper-sulfur-platinum bridges.}, number={24}, journal={Biochemistry}, publisher={American Chemical Society (ACS)}, author={Dolgova, Natalia V. and Yu, Corey and Cvitkovic, John P. and Hodak, Miroslav and Nienaber, Kurt H. and Summers, Kelly L. and Cotelesage, Julien J. H. and Bernholc, Jerzy and Kaminski, George A. and Pickering, Ingrid J. and et al.}, year={2017}, month={Jun}, pages={3129–3141} }
 @article{li_hodak_lu_bernholc_2017, title={Selective sensing of ethylene and glucose using carbon-nanotube-based sensors: an ab initio investigation}, volume={9}, ISSN={2040-3364 2040-3372}, url={http://dx.doi.org/10.1039/C6NR07371A}, DOI={10.1039/c6nr07371a}, abstractNote={Functionalized carbon nanotubes have great potential for nanoscale sensing applications, yet many aspects of their sensing mechanisms are not understood. Here, two paradigmatic sensor configurations for detection of biologically important molecules are investigated through ab initio calculations: a non-covalently functionalized nanotube for glucose detection and a covalently functionalized nanotube for ethylene detection. Glucose and ethylene control key life processes of humans and plants, respectively, despite of their structural and chemical simplicity. The sensors' electrical conductance and transmission coefficients are evaluated at the full density-functional theory level via the non-equilibrium Green's function method. We also investigate the effects of the density of the receptors, the band gaps of the nanotubes, the source-drain voltages, and the atomic modification of the receptor on detection sensitivities. A clear atomistic picture emerges about the mechanisms involved in glucose and ethylene sensing. While semiconducting nanotubes exhibit good sensitivities in both cases, the current through metallic nanotubes is only weakly affected by analyte attachment. These quantitative results could guide the design of improved sensors.}, number={4}, journal={Nanoscale}, publisher={Royal Society of Chemistry (RSC)}, author={Li, Yan and Hodak, Miroslav and Lu, Wenchang and Bernholc, J.}, year={2017}, pages={1687–1698} }
 @article{li_hodak_lu_bernholc_2016, title={Mechanisms of NH3 and NO2 detection in carbon-nanotube-based sensors: An ab initio investigation}, volume={101}, ISSN={0008-6223}, url={http://dx.doi.org/10.1016/j.carbon.2016.01.092}, DOI={10.1016/j.carbon.2016.01.092}, abstractNote={The mechanisms of NH3 and NO2 detection by single-walled carbon nanotube-based devices are investigated by ab initio calculations and the non-equilibrium Greens function (NEGF) methodology. While both NH3 and NO2 can physisorb to a pristine carbon nanotube, we show that their adsorption only results in small current changes through the device. For a carbon nanotube (CNT) attached to gold nanowire leads, the most sensitive detection site is at the CNT near the CNT-Au contact, where chemisorption occurs. The resulting change in electron transmission and low-bias current can lead to over 30% sensitivity. While both NH3 and NO2 can also chemisorb at the Au electrodes, their adsorption results in only a small change in the plurality of the conducting levels of the gold layers, and thus a small effect on current. In order to enhance the detection sensitivity, it is thus beneficial to mask the electrodes to prevent chemisorption. Furthermore, the length of the pure CNT segment does not strongly affect the relative sensitivity. Our results suggest that a short-CNT device with exposed contact regions and masked electrodes would have the greatest sensitivity.}, journal={Carbon}, publisher={Elsevier BV}, author={Li, Yan and Hodak, Miroslav and Lu, Wenchang and Bernholc, J.}, year={2016}, month={May}, pages={177–183} }
 @article{li_hodak_bernholc_2015, title={Enzymatic Mechanism of Copper-Containing Nitrite Reductase}, volume={54}, ISSN={0006-2960 1520-4995}, url={http://dx.doi.org/10.1021/bi5007767}, DOI={10.1021/bi5007767}, abstractNote={Copper-containing nitrite reductases (CuNiRs) catalyze the reduction of nitrite to nitric oxide, a key step in the denitrification process that maintains balance between organic and inorganic nitrogen. Despite their importance, their functioning is not well understood. In this work, we carry out first-principles calculations and show that the available structural data are consistent only with a single mechanism. For this mechanism, we determine the activation energies, transition states, and minimum energy pathways of CuNiR. The calculations lead to an updated enzymatic mechanism and resolve several controversial issues. In particular, our work identifies the origins of the two protons necessary for the enzymatic function and shows that the transformation from the initial O-coordination of substrate to the final N-coordination of product is achieved by electron transfer from T1 copper to T2 copper, rather than by the previously reported side-on coordination of a NO intermediate, which only takes place in the reduced enzyme. We also examine the role of structural change in the critical residue Asp(98), reported in one experimental study, and find that while the structural change affects the energetics of substrate attachment and product release at the T2 copper reaction center, it does not significantly affect the activation energy and reaction pathways of the nitrite reduction process.}, number={5}, journal={Biochemistry}, publisher={American Chemical Society (ACS)}, author={Li, Yan and Hodak, Miroslav and Bernholc, J.}, year={2015}, month={Jan}, pages={1233–1242} }
 @article{rose_hodak_bernholc_2011, title={Mechanism of copper(II)-induced misfolding of Parkinson's disease protein}, volume={1}, journal={Scientific Reports}, author={Rose, F. and Hodak, M. and Bernholc, J.}, year={2011} }
 @article{hodak_bernholc_2010, title={Insights into prion protein function from atomistic simulations}, volume={4}, ISSN={["1933-690X"]}, DOI={10.4161/pri.4.1.10969}, abstractNote={Computer simulations are a powerful tool for studies of biological systems. They have often been used to study prion protein (PrP), a protein responsible for neurodegenerative diseases, which include “mad cow disease” in cattle and Creutzfeldt-Jacob disease in humans. An important aspect of the prion protein is its interaction with copper ion, which is thought to be relevant for PrP’s yet undetermined function and also potentially play a role in prion diseases. For studies of copper attachment to the prion protein, computer simulations have often been used to complement experimental data and to obtain binding structures of Cu-PrP complexes. This paper summarizes the results of recent ab initio calculations of copper-prion protein interactions focusing on the recently discovered concentration-dependent binding modes in the octarepeat region of this protein. In addition to determining the binding structures, computer simulations were also used to make predictions about PrP’s function and the role of copper in prion diseases. The results demonstrate the predictive power and applicability of ab initio simulations for studies of metal-biomolecular complexes.}, number={1}, journal={PRION}, author={Hodak, Miroslav and Bernholc, Jerzy}, year={2010}, pages={13–19} }
 @article{hodak_chisnell_lu_bernholc_2009, title={Functional implications of multistage copper binding to the prion protein}, volume={106}, ISSN={0027-8424 1091-6490}, url={http://dx.doi.org/10.1073/pnas.0903807106}, DOI={10.1073/pnas.0903807106}, abstractNote={The prion protein (PrP) is responsible for a group of neurodegenerative diseases called the transmissible spongiform encephalopathies. The normal function of PrP has not yet been discovered, but indirect evidence suggests a linkage to its ability to bind copper. In this article, low-copper-concentration bindings of Cu2+ to PrP are investigated by using a recently developed hybrid density functional theory (DFT)/DFT method. It is found that at the lowest copper concentrations, the binding site consists of 4 histidine residues coordinating the copper through ε imidazole nitrogens. At higher concentrations, 2 histidines are involved in the binding, one of them in the axial position. These results are in good agreement with existing experimental data. Comparison of free energies for all modes of coordination shows that when enough copper is available, the binding sites will spontaneously rearrange to accommodate more copper ions, despite the fact that binding energy per copper ion decreases with concentration. These findings support the hypothesis that PrP acts as a copper buffer in vivo, protecting other proteins from the attachment of copper ions. Using large-scale classical molecular dynamics, we also probe the structure of full-length copper-bound PrP, including its unfolded N-terminal domain. The results show that copper attachment leads to rearrangement of the structure of the Cu-bonded octarepeat region and to development of turns in areas separating copper-bound residues. These turns make the flexible N-terminal domain more rigid and thus more resistant to misfolding. The last result suggests that copper binding plays a beneficial role in the initial stages of prion diseases.}, number={28}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Hodak, Miroslav and Chisnell, Robin and Lu, Wenchang and Bernholc, J.}, year={2009}, month={Jun}, pages={11576–11581} }
 @article{hodak_lu_bernholc_2008, title={Hybrid ab initio Kohn-Sham density functional theory/frozen-density orbital-free density functional theory simulation method suitable for biological systems}, volume={128}, number={1}, journal={Journal of Chemical Physics}, author={Hodak, M. and Lu, W. C. and Bernholc, J.}, year={2008} }
 @article{bernholc_hodak_lu_2008, title={Recent developments and applications of the real-space multigrid method}, volume={20}, number={29}, journal={Journal of Physics. Condensed Matter}, author={Bernholc, J. and Hodak, M. and Lu, W. C.}, year={2008} }
 @article{hodak_wang_lu_bernholc_2007, title={Implementation of ultrasoft pseudopotentials in large-scale grid-based electronic structure calculations}, volume={76}, ISSN={["2469-9969"]}, DOI={10.1103/physrevb.76.085108}, abstractNote={An implementation of Vanderbilt ultrasoft pseudopotentials in real-space grid-based electronic structure calculations is presented. Efficient utilization of these pseudopotentials requires the use of different grids for i wave functions, ii charge density, and iii sharply peaked operators within the atomic core radii. High-order interpolation between the various grids is important for accuracy, as is high-order discretization for the differential operators. However, efficiency is also of paramount importance, especially when parallelizing over hundreds or thousands of processors. We describe algorithms and procedures used to achieve an effective implementation in the real-space multigrid code, and provide test results for first-row diatomics, bulk transition metals, and energy-conserving quantum molecular dynamics of water. The code parallelizes efficiently over several thousands of processors on modern parallel supercomputers, such as the Cray XT3 and XT4.}, number={8}, journal={PHYSICAL REVIEW B}, author={Hodak, Miroslav and Wang, Shuchun and Lu, Wenchang and Bernholc, J.}, year={2007}, month={Aug} }
 @article{hodak_girifalco_2003, title={Systems of C-60 molecules inside (10,10) and (15,15) nanotube: A Monte Carlo study}, volume={68}, ISSN={["2469-9969"]}, DOI={10.1103/physrevb.68.085405}, abstractNote={We use Monte Carlo simulations to investigate properties of systems of ${\mathrm{C}}_{60}$ molecules inside (10,10) and (15,15) nanotubes. In the case of the (10,10) nanotube, ${\mathrm{C}}_{60}$ molecules form a quasi-one-dimensional system. The thermodynamical properties of this system such as energy and heat capacity are found to be very close to the properties of a one-dimensional system to which interaction with a nanotube is added. The structural properties are found to be insensitive to the quasi-one-dimensional nature of the system and are the same as those calculated for a one-dimensional system of ${\mathrm{C}}_{60}$ molecules. The transformation from a periodic to a nonperiodic state (``melting'') is a gradual one and cannot be detected through the heat capacity. Inside the (15,15) nanotube, a system of ${\mathrm{C}}_{60}$ molecules behaves differently. Most notably, the heat-capacity curve shows an extra peak when compared to the result for the (10,10) case. We show that this is due to the ``melting,'' i.e., transformation of a zigzag structure existing at low temperatures to a disordered one. We also show that systems with very high density $(g95%)$ do not show this peak and ``melt'' differently.}, number={8}, journal={PHYSICAL REVIEW B}, author={Hodak, M and Girifalco, LA}, year={2003}, month={Aug} }