Investigation of binding characteristics of ritonavir with calf thymus DNA with the help of spectroscopic techniques and molecular simulation
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
Authors: Kou, Song-Bo; Zhou, Kai-Li; Lin, Zhen-Yi; Lou, Yan-Yue; Wang, Bao-Li; Shi, Jie-Hua; Liu, Ying-Xin
Abstract
The binding behavior of ritonavir (RTV), a HIV/AIDS protease inhibitor, with ct-DNA was characterized through multiple testing technologies and theoretical calculation. The findings revealed that the RTV-DNA complex was formed through the noncovalent interaction mainly including conventional hydrogen bonds and carbon hydrogen bonds as well as hydrophobic interactions (pi-alkyl interactions). The stoichiometry and binding constant of the RTV-DNA complex were 1:1 and 1.87 x 10(3) M-1 at 298 K, respectively, indicating that RTV has moderate affinity with ct-DNA. The findings confirmed that RTV binds to the minor groove of DNA. The outcomes of CD experiments showed that the binding with RTV changed the conformation of DNA slightly. However, the conformation of RTV had obvious changes after binding to DNA, meaning that the flexibility of RTV molecule played an important role in stabilizing the RTV-DNA complex. Meanwhile, the results of DFT calculation revealed that the RTV and DNA interaction caused the changes in the frontier molecular orbitals, dipole moment and atomic charge distribution of RTV, altering the chemical properties of RTV when it bound to DNA. Communicated by Ramaswamy H. Sarma
A Century Later: Rural Public Health's Enduring Challenges and Opportunities
AMERICAN JOURNAL OF PUBLIC HEALTH
Authors: Ziller, Erika; Milkowski, Carly
Abstract
The US public health community has demonstrated increasing awareness of rural health disparities in the past several years. Although current interest is high, the topic is not new, and some of the earliest public health literature includes reports on infectious disease and sanitation in rural places. Continuing through the first third or the 20th century, dozens or articles documented rural disparities in infant and maternal mortality, sanitation and water safety, health care access, and among Black, Indigenous, and People of Color communities, Current rural research reveals similar challenges, and strategies suggested for addressing rural urban health disparities 100 years ago resonate today. This article examines rural public health Literature from a century ago and its connections to contemporary rural health disparities. We describe parallels between current and historical rural public health challenges and discuss how strategies proposed in the early 20th century may inform current policy and practice. As we explore the new frontier of rural public health, it is critical to consider enduring rural challenges and how to ensure that proposed solutions translate into actual health improvements.