Steps to the clinic with ELF EMF

Madkan, Ash; Blank, Martin; Elson, Edward C.; Chou, Kuo‐Chen; Geddis, Matthew S.; Goodman, Reba

doi:10.4236/ns.2009.13020

Cited by 30 publications

(11 citation statements)

References 83 publications

(102 reference statements)

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“…Since publication of the pioneer paper in 1977 [58], it has been established that low-frequency motions existing in proteins and DNA can help reveal dynamic mechanisms underlying fundamental biological functions [59][60][61][62][63]. NMR observation later confirmed such inferences and the findings were applied to medical treatments [64][65][66][67]. In recent years, application of molecular dynamics to investigate internal motions and biological functions of biomacromolecules has opened new frontiers.…”

Section: Author Summarymentioning

confidence: 99%

Two Birds with One Stone? Possible Dual-Targeting H1N1 Inhibitors from Traditional Chinese Medicine

2011

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The H1N1 influenza pandemic of 2009 has claimed over 18,000 lives. During this pandemic, development of drug resistance further complicated efforts to control and treat the widespread illness. This research utilizes traditional Chinese medicine Database@Taiwan (TCM Database@Taiwan) to screen for compounds that simultaneously target H1 and N1 to overcome current difficulties with virus mutations. The top three candidates were de novo derivatives of xylopine and rosmaricine. Bioactivity of the de novo derivatives against N1 were validated by multiple machine learning prediction models. Ability of the de novo compounds to maintain CoMFA/CoMSIA contour and form key interactions implied bioactivity within H1 as well. Addition of a pyridinium fragment was critical to form stable interactions in H1 and N1 as supported by molecular dynamics (MD) simulation. Results from MD, hydrophobic interactions, and torsion angles are consistent and support the findings of docking. Multiple anchors and lack of binding to residues prone to mutation suggest that the TCM de novo derivatives may be resistant to drug resistance and are advantageous over conventional H1N1 treatments such as oseltamivir. These results suggest that the TCM de novo derivatives may be suitable candidates of dual-targeting drugs for influenza.

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Section: Author Summarymentioning

confidence: 99%

Two Birds with One Stone? Possible Dual-Targeting H1N1 Inhibitors from Traditional Chinese Medicine

2011

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“…Many marvelous biological functions in proteins and DNA and their profound dynamic mechanisms, such as switch between active and inactive states [45], cooperative effects [46], allosteric transition [47,48], intercalation of drugs into DNA [49], and assembly of microtubules [50], can be revealed by studying their internal motions [51,52]. Likewise, to really understand the action mechanism of PPARs, we should consider not only the static structures concerned but also the dynamical information obtained by simulating their internal motions or dynamic process.…”

Section: Molecular Dynamics Simulationsmentioning

confidence: 99%

Analysis of Rate-limiting Long-range Contacts in the Folding Rate of Three-state and Two-state Proteins

Balasubramanian

Selvaraj²

2011

PPL

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In the past decade, when compared to models describing the folding rates of two-state proteins, models describing the folding mechanism of three-state proteins remain quite limited due to the complexity present in the folding mechanism and lack in their experimental data. In the present work, rate-limiting long-range contacts were classified into various bins based on sequence separation distance between the contacting residues and the role of these bins were analyzed for their importance in a data set of 35 three-state proteins. Predicting the folding rates of these proteins have been carried out by relating experimental folding rates and long-range contacts obtained from various sequence separation bins. For comparison, using the present model, prediction of the folding rates of 45 two-state proteins also resulted with good accuracy. Our method shows that long-range contacts observed in the final 3-D structure of proteins at various sequence separation bins are found to be an important descriptor in explaining the folding rates of three-state proteins and suggest that formation of contacts between residues present at these sequence separation distance may be a crucial factor in deciding structure formation and folding rates of these proteins. The aim of our present work is not to construct a new descriptor for the folding rates of three-state proteins, nor is to provide improved means of folding-rate prediction for these proteins. We tend to elucidate that how long-range contacts play a crucial role in the folding mechanism of three state proteins belonging to three major structural classes and implication of these observations due to rate-limiting long-range contacts has been discussed in the light of other experimental studies of protein folding.

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“…Furthermore, the low-frequency internal motions in proteins as originally inferred by Professor Chou in 1977 [65] have also been clearly observed in 2001 by NMR [89], and applied in medical treatments [90][91][92].…”

Section: Low-frequency Internal Motion In Biomolecules and Its Biologmentioning

confidence: 78%

Theoretical and experimental biology in one<br>—A symposium in honour of Professor Kuo-Chen Chou’s 50th anniversary and Professor Richard Giegé’s 40th anniversary of their scientific careers

Lin¹,

Lapointe²

2013

JBiSE

138

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It has been a dream that theoretical biology can be extensively applied in experimental biology to accelerate the understanding of the sophiscated movements in living organisms. A brave assay and an excellent example were represented by enzymology, in which the well-established physico-chemistry is used to describe, to fit, to predict and to improve enzyme reactions. Before the modern bioinformatics, the developments of the combination of theoretical biology and experimental biology have been mainly limited to various classic formulations. The systematic use of graphic rules by Prof. Kuo-Chen Chou and his coworkers has significantly facilitated to deal with complicated enzyme systems. With the recent fast progress of bioinformatics, prediction of protein structures and various protein attributes have been well established by Chou and co-workers, stimulating the experimental biology. For example, their recent method for predicting protein subcellular localization (one of the important attributes of proteins) has been extensively applied by scientific colleagues, yielding many new results with thousands of citations. The research by Prof. Chou is characterized by introducing novel physical concepts as well as powerful and elegant mathematical methods into important biomedical problems, a focus throughout his career, even when facing enormous difficulties. His efforts in 50 years have greatly helped us to realize the dream to make "theoretical and experimental biology in one". Prof. Richard Giege is well known for his multidisciplinary research combining physics, chemistry, enzymology and molecular biology. His major focus of study is on the identity of tRNAs and their interactions with aminoacyl-tRNA synthetases (aaRS), which are of critical importance to the fidelity of protein biosynthesis. He and his colleagues have carried out the first crystallization of a tRNA/aaRS complex, that between tRNA Asp and AspRS from yeast. The determination of the complex structure contributed significantly to understand the interaction of protein and RNA. From his fine research, they have also found other biological function of these small RNAs. He has developed in parallel appropriate methods for his research, of which the protein crystallogenesis, a name he has coined, is an excellent example. Now macromolecular crystallogenesis has become a developed science. In fact, such contribution has accelerated the development of protein crystallography, stimulating the study of macromolecular structure and function.

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Steps to the clinic with ELF EMF

Cited by 30 publications

References 83 publications

Two Birds with One Stone? Possible Dual-Targeting H1N1 Inhibitors from Traditional Chinese Medicine

Two Birds with One Stone? Possible Dual-Targeting H1N1 Inhibitors from Traditional Chinese Medicine

Analysis of Rate-limiting Long-range Contacts in the Folding Rate of Three-state and Two-state Proteins

Theoretical and experimental biology in one<br>—A symposium in honour of Professor Kuo-Chen Chou’s 50th anniversary and Professor Richard Giegé’s 40th anniversary of their scientific careers

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Steps to the clinic with ELF EMF

Cited by 30 publications

References 83 publications

Two Birds with One Stone? Possible Dual-Targeting H1N1 Inhibitors from Traditional Chinese Medicine

Two Birds with One Stone? Possible Dual-Targeting H1N1 Inhibitors from Traditional Chinese Medicine

Analysis of Rate-limiting Long-range Contacts in the Folding Rate of Three-state and Two-state Proteins

Theoretical and experimental biology in one&lt;br&gt;—A symposium in honour of Professor Kuo-Chen Chou’s 50th anniversary and Professor Richard Gieg&#233;’s 40th anniversary of their scientific careers

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Theoretical and experimental biology in one<br>—A symposium in honour of Professor Kuo-Chen Chou’s 50th anniversary and Professor Richard Giegé’s 40th anniversary of their scientific careers