Browsing by Author "Zhang, Yuqi"
Results Per Page
Sort Options
Item Open Access A Symphony of Charge Transfer Theory, Conductive DNA Junction Modeling and Chemical Library Design(2016) Zhang, YuqiBiological electron transfer (ET) reactions are typically described in the framework of coherent two-state electron tunneling or multi-step hopping. Yet, these ET reactions may involve multiple redox cofactors in van der Waals contact with each other and with vibronic broadenings on the same scale as the energy gaps among the species. In this regime, fluctuations of the molecule and its medium can produce transient energy level matching among multiple electronic states. This transient degeneracy, or flickering electronic resonance among states, is found to support coherent (ballistic) charge transfer. Importantly, ET rates arising from a flickering resonance (FR) mechanism will decay exponentially with distance because the probability of energy matching multiple states is multiplicative. The distance dependence of FR transport thus mimics the exponential decay that is usually associated with electron tunneling, although FR transport involves real carrier population on the bridge and is not a tunneling phenomenon. Likely candidates for FR transport are macromolecules with ET groups in van der Waals contact: DNA, bacterial nanowires, multi-heme proteins, strongly coupled porphyrin arrays, and proteins with closely packed redox-active residues. The theory developed here is used to analyze DNA charge-transfer kinetics, and we find that charge transfer distances up to 3-4 bases may be accounted for with this mechanism. Thus, the observed rapid (exponential) distance dependence of DNA ET rates over distances of ≲10 Å does not necessarily prove a tunneling mechanism.
Molecular structures that direct charge transport in two or three dimensions could help to enable the development of molecule-based electrical switches and gates. As a step toward this goal, we use theory, modeling and simulation to explore DNA three-way junctions (TWJs). Molecular dynamics (MD) simulations and quantum calculations, indicate that DNA TWJs undergo dynamic interconversion among “well stacked” conformations on the time scale of nanoseconds, a feature that makes the junctions very different from linear DNA duplexes. The studies further indicate that this conformational gating would control charge flow through these TWJs, distinguishing them from conventional (larger size scale) gated devices. Simulations also find that structures with polyethylene glycol (PEG) linking groups (“extenders”) lock conformations that favor CT for 25 ns or more. The simulations explain the kinetics observed experimentally in TWJs and rationalize their transport properties compared to double-stranded DNA. Furthermore, we redesigned DNA TWJs that have equally coupled output pathways for charge. The TWJ was also designed to switch between the two conductive states in responsive to an applied electric field.
Computationally aided drug discovery confronts the problem to balance performance and computation cost. Earlier study reveals that a less-expensive docking approach is not reliable to estimate the protein-ligand affinity in exploring drug candidates targeting CARM1 (coactivator-associated arginine methyltransferase 1). However, more accurate binding free energy calculation based on molecular dynamics sampling is not affordable in a high throughput screening. A truncated MD method was developed and can be used to estimate the binding free energy with similar accuracy with the full-system MD methods, while reducing the computation cost ten fold. Thus, this truncated MD method is feasible in a high throughput screening towards drug discovery.
Item Open Access Association Between Hospital Monopoly Status, Patient Socioeconomic Disadvantage, and Total Joint Arthroplasty Price Disclosure.(The Journal of the American Academy of Orthopaedic Surgeons, 2023-10) Peairs, Emily M; Zhang, Gloria X; Kerr, David; Erickson, Melissa M; Zhang, Yuqi; Cerullo, MarceloIntroduction
In recent years, healthcare institutions and regulatory bodies have enacted cost transparency mandates for routine interventions such as total hip arthroplasty and total knee arthroplasty. However, disclosure rates remain low. This study examined the effect of financial characteristics of hospitals and the socioeconomic status of patients on price disclosure.Methods
Hospitals conducting total hip arthroplasty/total knee arthroplasty, their quality ratings, and procedural volumes were identified using the Leapfrog Hospital Survey and linked to procedure-specific prices. Financial performance and the Area Deprivation Index (ADI) were used to correlate disclosure rates with hospital and patient characteristics. Hospital financial, operational, and patient summary statistics were compared by price-disclosure status using two-sample t -tests for continuous variables and Pearson chi-square test for categorical variables. The association between total joint arthroplasty price disclosure and hospital ADI was further evaluated using modified Poisson regression.Results
A total of 1,425 hospitals certified by the Centers for Medicare & Medicaid Services were identified in the United States. 50.5% (n = 721) of hospitals had no published payer-specific price information. Hospitals in an area of higher socioeconomic disadvantage were more likely to disclose prices of total joint arthroplasty (incidence rate ratio = 0.966, 95% CI: 0.937 to 0.995, P = 0.024). Hospitals that were considered monopolies or were for-profit were less likely to disclose prices (IRR = 1.15, 95% CI: 1.030 to 1.280, P = 0.01; IRR = 1.256, 95% CI: 0.986 to 1.526, P = 0.038, respectively). When accounting for both ADI and monopoly status, hospitals with patients who had a higher ADI were more likely to disclose costs for a total joint arthroplasty, whereas for-profit hospitals or hospitals considered monopolies in their HSA were less likely to disclose prices.Discussion
For nonmonopoly hospitals, a higher ADI correlated with a higher likelihood of price disclosure. However, for monopoly hospitals, there was no significant association between ADI and price disclosure.Level of evidence
II.