A Comprehensive Model for the Recognition of Human Telomeres by TRF1

Garton, Michael; Laughton, Charles A.

doi:10.1016/j.jmb.2013.05.005

Cited by 15 publications

(14 citation statements)

References 34 publications

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“…This finding has recently been supported by all-atom molecular dynamics (MD) studies of homeodomain and Zn-finger complexes with DNA ( 25 ). Another aspect of protein–DNA interface dynamics is illustrated in a recent MD study of telomere repeat binding factors (TRF1 and TRF2), where the dynamics of individual amino acids chains suggested that they could contribute to the recognition of more than one base pair, helping to resolve conflicting experimental data ( 26 ).…”

Section: Introductionmentioning

confidence: 99%

Dynamics and recognition within a protein–DNA complex: a molecular dynamics study of the SKN-1/DNA interaction

2015

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Molecular dynamics simulations of the Caenorhabditis elegans transcription factor SKN-1 bound to its cognate DNA site show that the protein–DNA interface undergoes significant dynamics on the microsecond timescale. A detailed analysis of the simulation shows that movements of two key arginine side chains between the major groove and the backbone of DNA generate distinct conformational sub-states that each recognize only part of the consensus binding sequence of SKN-1, while the experimentally observed binding specificity results from a time-averaged view of the dynamic recognition occurring within this complex.

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Section: Introductionmentioning

confidence: 99%

Dynamics and recognition within a protein–DNA complex: a molecular dynamics study of the SKN-1/DNA interaction

2015

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“…In addition, overexpression of the telomeric repeat binding factor 1 ( TERF1 ) gene reduced telomere-associated DNA damage foci and pro-inflammatory cytokine expression in aging endothelial cells [ 23 ]. As TERF1 gene encodes a protein that maintains telomere length,[ 24 ] this finding may suggest a protective effect of longer telomeres on the senescence of endothelial cells in the vascular system.…”

Section: Discussionmentioning

confidence: 99%

Impact of biological aging on arterial aging in American Indians: findings from the Strong Heart Family Study

Peng

Zhu

Yeh

et al. 2016

Aging

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Telomere length, a marker of biological aging, has been associated with cardiovascular disease (CVD). Increased arterial stiffness, an indicator of arterial aging, predicts adverse CVD outcomes. However, the relationship between telomere length and arterial stiffness is less well studied. Here we examined the cross-sectional association between leukocyte telomere length (LTL) and arterial stiffness in 2,165 American Indians in the Strong Heart Family Study (SHFS). LTL was measured by qPCR. Arterial stiffness was assessed by stiffness index β. The association between LTL and arterial stiffness was assessed by generalized estimating equation model, adjusting for sociodemographics (age, sex, education level), study site, metabolic factors (fasting glucose, lipids, systolic blood pressure, and kidney function), lifestyle (BMI, smoking, drinking, and physical activity), and prevalent CVD. Results showed that longer LTL was significantly associated with a decreased arterial stiffness (β=-0.070, P=0.007). This association did not attenuate after further adjustment for hsCRP (β=-0.071, P=0.005) or excluding participants with overt CVD (β=-0.068, P=0.012), diabetes (β=-0.070, P=0.005), or chronic kidney disease (β=-0.090, P=0.001). In summary, shorter LTL was significantly associated with an increased arterial stiffness, independent of known risk factors. This finding may shed light on the potential role of biological aging in arterial aging in American Indians.

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“…Center: A supercoiled 336‐base pair DNA microcircle . Right: The 2:1 complex between the shelterin protein TRF1 and a 19 base pair DNA duplex…”

Section: Nucleic Acid Structure and Recognitionmentioning

confidence: 99%

Biomolecular simulations: From dynamics and mechanisms to computational assays of biological activity

Huggins

Biggin

Dämgen

et al. 2018

WIREs Comput Mol Sci

148

142

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development, combining different levels of theory to increase accuracy, aiming to connect chemical and molecular changes to macroscopic observables. In this review, we outline biomolecular simulation methods and highlight examples of its application to investigate questions in biology. enzyme, membrane, molecular dynamics, multiscale, protein, QM/MM 1 | INTRODUCTION Biomolecular simulations are now making significant contributions to a wide variety of problems in drug discovery, drug development, biocatalysis, biotechnology, nanotechnology, chemical biology, and medicine. Biomolecular simulation is a rapidly growing field in scale and impact, increasingly demonstrating its worth in understanding mechanisms and analyzing activities, and contributing to the design of drugs and biocatalysts. Physics-based simulations complement experiments in building a molecular-level understanding of biology: They can test hypotheses and interpret and analyze experimental data in terms of interactions at the atomic level. Different types of simulation techniques have been developed, which are applicable to a range of different problems in biomolecular science. Simulations have already shown their worth in helping to analyze how enzymes catalyze biochemical reactions, and how proteins adopt their functional structures, for example, within cell membranes. They contribute to the design of drugs and catalysts, and in understanding the molecular basis of disease. Simulations have played a key role in developing the conceptual framework now at the heart of biomolecular science: that the dynamics of biological molecules is central to their function. Developing methods from chemical physics and computational science will open exciting new opportunities in biomolecular science, including in drug design and development, biotechnology, and biocatalysis. With high-performance computing resources, large-scale atomistic simulations of biological machines such as the ribosome, proton pumps and motors, membrane receptor complexes, and even whole viruses have become possible. Useful simulations of smaller systems can be carried out with desktop resources, thanks to developments allowing, for example, graphics processing units (GPUs) to be used. A particular challenge across the field is the integration of simulations crossing the span of length-and timescales as different types of simulation method are required for different types of problems. 1 Biomolecular systems pose fundamental scientific challenges (e.g., protein folding, enzyme catalysis, gene regulation, disease mechanisms, and antimicrobial resistance) and are at the heart of many advanced technological developments (drug discovery, biotechnology, biocatalysis, biomaterials, and genetic engineering). Biomolecular systems are inherently complex and pose significant challenges in modeling. An essential underlying paradigm is the need to consider biomolecular ensembles and their dynamics, rather than simply static biomolecular structures to understand and predict their behavior and propertie...

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A Comprehensive Model for the Recognition of Human Telomeres by TRF1

Cited by 15 publications

References 34 publications

Dynamics and recognition within a protein–DNA complex: a molecular dynamics study of the SKN-1/DNA interaction

Dynamics and recognition within a protein–DNA complex: a molecular dynamics study of the SKN-1/DNA interaction

Impact of biological aging on arterial aging in American Indians: findings from the Strong Heart Family Study

Biomolecular simulations: From dynamics and mechanisms to computational assays of biological activity

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