Dynamic Equilibria of Short-Range Electrostatic Interactions at Molecular Interfaces of Protein–DNA Complexes

Intermolecular ion pairs (salt bridges) are crucial for protein–DNA association. For two protein–DNA complexes, we demonstrate that the ion pairs of protein side-chain NH₃⁺ and DNA phosphate groups undergo dynamic transitions between distinct states in which the charged moieties are either in direct contact or separated by water. While the crystal structures of the complexes show only the solvent-separated ion pair (SIP) state for some interfacial lysine side chains, our NMR hydrogen-bond scalar coupling data clearly indicate the presence of the contact ion pair (CIP) state for the same residues. The 0.6-μs molecular dynamics (MD) simulations confirm dynamic transitions between the CIP and SIP states. This behavior is consistent with our NMR order parameters and scalar coupling data for the lysine side chains. Using the MD trajectories, we also analyze the free energies of the CIP–SIP equilibria. This work illustrates the dynamic nature of short-range electrostatic interactions in DNA recognition by proteins

Superior success rate of intracavitary electrocardiogram guidance for peripherally inserted central catheter placement in patients with cancer: A randomized open-label controlled multicenter study

<div><p>Background</p><p>Intracavitary electrocardiogram (IC ECG) guidance emerges as a new technique for peripherally inserted central catheters (PICCs) placement and demonstrates many potential advantages in recent observational studies.</p><p>Aims</p><p>To determine whether IC ECG-guided PICCs provide more accurate positioning of catheter tips compared to conventional anatomical landmarks in patients with cancer undergoing chemotherapy.</p><p>Methods</p><p>In this multicenter, open-label, randomized controlled study (ClinicalTrials.gov number, NCT02409589), a total of 1,007 adult patients were assigned to receive either IC ECG guidance (n = 500) or anatomical landmark guidance (n = 507) for PICC positioning. The confirmative catheter tip positioning x-ray data were centrally interpreted by independent radiologists. All reported analyses in the overall population were performed on an intention-to-treat basis. Analyses of pre-specified subgroups and a selected large subpopulation were conducted to explore consistency and accuracy.</p><p>Results</p><p>In the IC ECG-guided group, the first-attempt success rate was 89.2% (95% confidence interval [CI], 86.5% to 91.9%), which was significantly higher than 77.4% (95% CI, 73.7% to 81.0%) in the anatomical landmark group (P < 0.0001). This trend of superiority of IC ECG guidance was consistently noted in almost all prespecified patient subgroups and two selected large subpopulations, even when using optimal target rates for measurement. In contrast, the superiority nearly disappeared when PICCs were used via the left instead of right arms (interaction P-value = 0.021). No catheter-related adverse events were reported during the PICC intra-procedures in either group.</p><p>Conclusions</p><p>Our findings indicated that the IC ECG-guided method had a more favorable positioning accuracy versus traditional anatomical landmarks for PICC placement in adult patients with cancer undergoing chemotherapy. Furthermore, there were no significant safety concerns reported for catheterization using the two techniques.</p></div

Demographic details, smoking statuses, and activity levels of the study participants (ITT, N = 1,007).

<p>Demographic details, smoking statuses, and activity levels of the study participants (ITT, N = 1,007).</p

Catheter tip placement at first attempt and corresponding rates of outcome measures (ITT, N = 1,007).

<p>Catheter tip placement at first attempt and corresponding rates of outcome measures (ITT, N = 1,007).</p

First-attempt success rates with IC ECG versus landmark technique according to prespecified subgroups.

<p>First-attempt success rates with IC ECG versus landmark technique according to prespecified subgroups.</p