Molecular dynamics simulation and free energy calculation studies of the binding mechanism of allosteric inhibitors with TrkA kinase

Wu, Xia; Li, Qinlan; Wan, Shanhe; Zhang, Jiajie

doi:10.1080/07391102.2019.1708798

Cited by 8 publications

(6 citation statements)

References 24 publications

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“…The initial coordinates of the ACE-PPLLFAAL complexes for molecular dynamics (MD) simulations were chosen using the criterion of the lowest energy of the complex combined with visual inspection [53]. The MD simulations were performed using Amber software(Amber 20, University of California, San Francisco, CA, US) on the Yinfo Cloud Computing Platform (http://www.yinfotek.com/platform, 20 October 2021) with the parameters set according to Jiang et al [54].…”

Section: Molecular Simulationsmentioning

confidence: 99%

A Novel Angiotensin-I-Converting Enzyme (ACE) Inhibitory Peptide from Takifugu flavidus

Chen

Cai

et al. 2021

Marine Drugs

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Alcalase, neutral protease, and pepsin were used to hydrolyze the skin of Takifugu flavidus. The T. flavidus hydrolysates (TFHs) with the maximum degree of hydrolysis (DH) and angiotensin-I-converting enzyme (ACE)-inhibitory activity were selected and then ultra-filtered to obtain fractions with components of different molecular weights (MWs) (<1, 1–3, 3–10, 10–50, and >50 kDa). The components with MWs < 1 kDa showed the strongest ACE-inhibitory activity with a half-maximal inhibitory concentration (IC50) of 0.58 mg/mL. Purification and identification using semi-preparative liquid chromatography, Sephadex G-15 gel chromatography, RP-HPLC, and LC–MS/MS yielded one new potential ACE-inhibitory peptide, PPLLFAAL (non-competitive suppression mode; IC50 of 28 μmmol·L−1). Molecular docking and molecular dynamics simulations indicated that the peptides should bind well to ACE and interact with amino acid residues and the zinc ion at the ACE active site. Furthermore, a short-term assay of antihypertensive activity in spontaneously hypertensive rats (SHRs) revealed that PPLLFAAL could significantly decrease the systolic blood pressure (SBP) and diastolic blood pressure (DBP) of SHRs after intravenous administration. These results suggested that PPLLFAAL may have potential applications in functional foods or pharmaceuticals as an antihypertensive agent.

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Section: Molecular Simulationsmentioning

confidence: 99%

A Novel Angiotensin-I-Converting Enzyme (ACE) Inhibitory Peptide from Takifugu flavidus

Chen

Cai

et al. 2021

Marine Drugs

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“…In vitro glycation of DNA was done and characterized, as previously described 48 . To summarize, DNA (20 ng/µl final concentration) from the blood of non-diabetic individuals was incubated with 25 mM fructose at 37 °C for 5, 10, and 15 days in the presence or absence of RA (25 µM final concentration) in phosphate buffer saline (PBS).…”

Section: Methodsmentioning

confidence: 99%

Rosmarinic acid inhibits DNA glycation and modulates the expression of Akt1 and Akt3 partially in the hippocampus of diabetic rats

Alrubaye

Motovali-Bashi

Miroliaei

2021

Sci Rep

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Non-enzymatic glycation of DNA and the associated effects are among pathogenic factors in diabetes mellitus. Natural polyphenols have anti-diabetic activity. Herein, the protective role of one of the phytochemicals, rosmarinic acid (RA), was evaluated in glycation (with fructose) of human DNA and expression of Akt genes in the hippocampus of diabetic rats. In-vitro studies using fluorescence, agarose gel electrophoresis, fluorescence microscopy, and thermal denaturation analyses revealed that glycation causes DNA damage and that RA inhibits it. In-vivo studies were performed by induction of diabetes in rats using streptozotocin. The diabetic rats were given RA daily through gavage feeding. The expression of Akt genes (inhibitors of apoptosis) in the hippocampus was evaluated using RT-qPCR. In diabetic rats, Akt1 and Akt3 were significantly down-regulated compared to the control group. Treating the diabetic rats with RA returned the expression of Akt1 and Akt3 relatively to the normal condition. Past studies have shown that diabetes induces apoptosis in the hippocampal neurons. Given that glycation changes the genes expression and causes cell death, apoptosis of the hippocampal neurons can be due to the glycation of DNA. The results also suggest that RA has reliable potency against the gross modification of DNA under hyperglycemic conditions.

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“…The Trk receptor family comprises three transmembrane receptors TrkA, TrkB, and TrkC. TrkA is a high-affinity catalytic receptor for NGF and has been proven to be a promising target for chronic pain development [ 139 ]. The binding of NGF to TrkA activates intracellular signaling systems that transmit signals to the nucleus for transport to DRG cell bodies, thereby activating downstream signaling systems that mediate pain development.…”

Section: Nociceptive Channelsmentioning

confidence: 99%

Autonomic Nervous System Dysfunction Is Related to Chronic Prostatitis/Chronic Pelvic Pain Syndrome

Luo

Qian

et al. 2024

World J Mens Health

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Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a common and non-lethal urological condition with painful symptoms. The complexity of CP/CPPS’s pathogenesis and lack of efficient etiological diagnosis results in incomplete treatment and recurrent episodes, causing long-term mental and psychological suffering in patients. Recent findings indicate that the autonomic nervous system involves in CP/CPPS, including sensory, sympathetic, parasympathetic, and central nervous systems. Neuro-inflammation and sensitization of sensory nerves lead to persistent inflammation and pain. Sympathetic and parasympathetic alterations affect the cardiovascular and reproductive systems and the development of prostatitis. Central sensitization lowers pain thresholds and increases pelvic pain perception in chronic prostatitis. Therefore, this review summarized the detailed processes and mechanisms of the critical role of the autonomic nervous system in developing CP/CPPS. Furthermore, it describes the neurologically relevant substances and channels or receptors involved in this process, which provides new perspectives for new therapeutic approaches to CP/CPPS.

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Molecular dynamics simulation and free energy calculation studies of the binding mechanism of allosteric inhibitors with TrkA kinase

Cited by 8 publications

References 24 publications

A Novel Angiotensin-I-Converting Enzyme (ACE) Inhibitory Peptide from Takifugu flavidus

A Novel Angiotensin-I-Converting Enzyme (ACE) Inhibitory Peptide from Takifugu flavidus

Rosmarinic acid inhibits DNA glycation and modulates the expression of Akt1 and Akt3 partially in the hippocampus of diabetic rats

Autonomic Nervous System Dysfunction Is Related to Chronic Prostatitis/Chronic Pelvic Pain Syndrome

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