Abstract:
:G protein coupled receptors (GPCRs) are a large eukaryotic protein family of transmembrane receptors that react to a signal coming from the extracellular environment to generate an intracellular response through the activation of a signal transduction pathway mediated by a heterotrimeric G protein. Their diversity, dictated by the multiplicity of stimuli to which they respond and by the variety of intracellular signalling pathways they activate, make them one of the most prominent families of validated pharmacological targets in biomedicine. In recent years, major breakthroughs in structure determination of GPCRs have given new stimuli to the exploration of the biology of these proteins, providing a structural basis to understand the molecular origin of GPCR mechanisms of action. Based on the information coming from these structural studies, a number of recent in silico investigations used molecular dynamics (MD) simulations to contribute to our knowledge of GPCRs. In this review, we will focus on investigations that, taking advantage of the tremendous progress in both hardware and software, made testable hypotheses that have been validated by subsequent structural studies. These stateof- the-art molecular simulations highlight the potential of microsecond MD simulations as a valuable tool in GPCR structural biology and biophysics.
journal_name
Curr Med Chemjournal_title
Current medicinal chemistryauthors
Vanni S,Rothlisberger Udoi
10.2174/092986712799320493subject
Has Abstractpub_date
2012-01-01 00:00:00pages
1135-45issue
8eissn
0929-8673issn
1875-533Xpii
CMC-EPUB-20120201-009journal_volume
19pub_type
杂志文章,评审abstract::Histone deacetylase inhibitors have generated significant interest as anti-cancer agents due to their ability to cause growth arrest, terminal differentiation and/ or apoptosis in carcinoma cells. Abbott entered this area after the serendipitous discovery of the biaryl hydroxamate A-161906 in a TGF beta mimetic screen...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/0929867033456576
更新日期:2003-11-01 00:00:00
abstract::The COVID-19 pandemic has had catastrophic Global effects on financial markets, jobs and peoples' lives. Future prevention/therapy of COVID-19 will rely heavily on vaccine development and attempts to repurpose drugs previously used for other microbial diseases. Little attention, however, has been paid to possible diff...
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abstract::Neural differentiation of embryonic stem cells (ESC) is considered a promising model to perform in vitro testing for neuroactive and neurotoxic compounds. We studied the potential of a dual reporter murine ESC line to identify bioactive and/or toxic compounds. This line expressed firefly luciferase under the control o...
journal_title:Current medicinal chemistry
pub_type: 杂志文章
doi:10.2174/092986713804999330
更新日期:2013-01-01 00:00:00
abstract::Chagas disease is one of the most important parasitic diseases in Latin America, affecting 16 to 18 million people. Nifurtimox and Benznidazol are drugs that are commonly used in its treatment; however, these drugs produce several adverse reactions and are not effective in the chronic phase of the disease. Therefore, ...
journal_title:Current medicinal chemistry
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doi:10.2174/092986709788803303
更新日期:2009-01-01 00:00:00
abstract::Statins are inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA reductase), the rate-limiting enzyme of cholesterol synthesis. In recent years, statins have become the major choice of treatment for hypercholesterolemia. Emerging evidence from both animal and human studies indicates that mechanisms i...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/0929867033457205
更新日期:2003-08-01 00:00:00
abstract::Type 2 diabetes mellitus (DM) is a public health burden and its co-existence with hypertension is long established in the context of the metabolic syndrome. Both DM and hypertension are major risk factors, for end-stage renal disease, cardiovascular events and mortality. Strict blood pressure (BP) control in diabetics...
journal_title:Current medicinal chemistry
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abstract::ATP-sensitive K(+) channels (K(ATP)channels) regulate insulin secretion by coupling intracellular metabolic changes to excitability of the plasma membrane in pancreatic beta-cells. The channels are closed when extracellular glucose levels are elevated due to enhanced feature. By contrast, cardiac-type K(ATP) channels,...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
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更新日期:2003-02-01 00:00:00
abstract::The present article reviews interesting cationic liposomes (cationic transfection lipids) with novel cationic cholesterol derivatives, a new strategy in gene transfection developed by our group and the presently accepted molecular mechanism of gene transfection. Use of confocal laser scanning microscopy and atomic for...
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更新日期:2003-07-01 00:00:00
abstract::MicroRNAs (miRNAs) translationally repressing their target messenger RNAs due to their gene-regulatory functions play an important but not unexpected role in a tumour development. More surprising are the findings that levels of various miRNAs are well correlated with presence of specific tumours and formation of metas...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
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更新日期:2013-01-01 00:00:00
abstract:BACKGROUND:During lead identification and optimization, the advancement criteria may be driven based on scientific principles, prior experiences, and/or by examining the path paved by approved drugs. However, accessing the discovery data on physicochemical and ADME properties of the approved kinase inhibitors is a monu...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
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更新日期:2017-01-01 00:00:00
abstract::Four different types of small RNAs functionally associated with gene silencing have been discovered in animals including small interfering RNAs (siRNAs), microRNAs (miRNAs), and Piwi-interacting RNAs (piRNAs). Experimental evidence suggests that miRNAs regulate the expression of more than 30% of protein-coding genes. ...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/092986710794182980
更新日期:2010-01-01 00:00:00
abstract::Chagas disease is an infectious tropical disease included within the group of neglected tropical diseases. Though historically endemic to Latin America, it has lately spread to high-income countries due to human migration. At present, there are only two available drugs, nifurtimox and benznidazole, approved for this t...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/0929867326666191016114839
更新日期:2020-01-01 00:00:00
abstract::Angiotensin converting enzyme (ACE) 2 is a homologue of ACE that catalyzes the conversion of Angiotensin (Ang) II into Ang1-7, which induces vasodilation, anti-fibrotic, anti-proliferative and anti-inflammatory effects. Given that ACE2 counterbalances the effects of Ang II, it has been proposed as a biomarker in kidne...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
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更新日期:2017-01-01 00:00:00
abstract::Inflammation plays a critical role in the atherosclerotic process in various vascular beds, starting from endothelial dysfunction and counting all stages of plaque development. The significant contribution of inflammation in the initiation and progression of atherosclerosis has been documented over many years but its ...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
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更新日期:2015-01-01 00:00:00
abstract::HIV-1 non-nucleoside reverse transcriptase inhibitors (NNRTIs) nowadays represent most promising anti-AIDS drugs that specifically inhibit HIV-1 reverse transcriptase (RT). They have a unique antiviral potency, high specificity and low cytotoxicity. However, to a great extent, the efficacy of HIV-1 NNRTIs is compounde...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
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更新日期:2011-01-01 00:00:00
abstract:BACKGROUND:Chronic Liver Disorders (CLD), caused by the lifestyle patterns like alcoholism or by non-alcoholic fatty liver disease or because of virus-mediated hepatitis, affect a large population fraction across the world. CLD progresses into end-stage diseases with a high mortality rate. Liver transplant is the only ...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
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更新日期:2020-01-01 00:00:00
abstract::Nature continues to be the main source of inspiration for synthetic chemists in their quest to make novel conjugates, which can have different physical, biological and medicinal properties. Nature makes these conjugates from mixed biosynthesis and some of these chimeras are found to exhibit unusual biological properti...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/092986706776055562
更新日期:2006-01-01 00:00:00
abstract::Bone pain arising from secondary skeletal malignancy constitutes one of the most common types of chronic pain among patients with cancer which can lead to rapid deterioration of the quality of life. Radionuclide therapy using bone-seeking radiopharmaceuticals based on the concept of localization of the agent at bone m...
journal_title:Current medicinal chemistry
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doi:10.2174/0929867326666190201142814
更新日期:2020-01-01 00:00:00
abstract::Complement plays a vital role in our innate immune defense against invasive microorganisms. Excessive complement activation or insufficient control of activation on host cells, however, is associated with several chronic disorders. Essential to the activation and amplification of the Alternative Pathway (AP) of comple...
journal_title:Current medicinal chemistry
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更新日期:2020-01-01 00:00:00
abstract:BACKGROUND:Since the serendipitous discovery of the antitumor activity of cisplatin there has been a continuous surge in studies aimed at the development of new cytotoxic metal complexes. While the majority of these complexes have been designed to interact with nuclear DNA, other targets for anticancer metallodrugs att...
journal_title:Current medicinal chemistry
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更新日期:2019-01-01 00:00:00
abstract:: ...
journal_title:Current medicinal chemistry
pub_type: 社论
doi:10.2174/092986732533181024105316
更新日期:2018-01-01 00:00:00
abstract::Despite the protective role of diets rich in fruit plant polyphenols against some cancers and chronic degenerative and inflammatory diseases, insufficient emphasis has been placed on oral health. Numerous studies have aimed to ascertain the role of polyphenols in the prevention and treatment of oral diseases; however,...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
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更新日期:2012-01-01 00:00:00
abstract::In recent years there has been a growing interest in computer-based screening. One of the driving forces has been the increased efficiency of protein crystallography leading to the real possibility of using structure-based design as a significant contributor to the discovery of novel ligands. In 1957 after 22 years of...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
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更新日期:2003-05-01 00:00:00
abstract:BACKGROUND:Hepatocellular Carcinoma (HCC) is one of the greatest global health burdens because of its uncontrolled cell growth and proliferation, aggressive nature as well as inherited chemoresistance. In spite of different treatment options currently available for HCC, the 5-year relative survival rates for HCC patien...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
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更新日期:2020-01-01 00:00:00
abstract:BACKGROUND:Vaccines are very effective medical tools for disease prevention and life span increase. Controversies have raised concern about their safety, from autism to polio vaccine contamination with simian virus 40 (SV-40). Hysteria surrounding vaccine-associated risks has resulted in a declining number of vaccinati...
journal_title:Current medicinal chemistry
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更新日期:2018-01-01 00:00:00
abstract:BACKGROUND:Numerous studies have demonstrated that halogenated agents elicit myocardial conditioning effects when adminis-tered perioperatively in cardiac surgery. Recent evidence has been published of the benefits of maintaining exposure to halogenated agents during the early postoperative period. The enzymatic mechan...
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更新日期:2020-10-01 00:00:00
abstract::The development of new drugs with potential therapeutic applications is one of the most complex and difficult process in the pharmaceutical industry. Millions of dollars and man-hours are devoted to the discovery of new therapeutical agents. As, the activity of a drug is the result of a multitude of factors such as bi...
journal_title:Current medicinal chemistry
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更新日期:2000-02-01 00:00:00
abstract::Since the discovery of penicillin, natural and synthetic β-lactams have aroused great interest not only as sources of effective antibacterial agents but also as specific inhibitors of proteases responsible for various non-bacterial pathological processes. This interest was reflected in our review published in Current ...
journal_title:Current medicinal chemistry
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更新日期:2014-01-01 00:00:00
abstract::It is well recognised that increased levels of high density lipoprotein (HDL) protect against atherosclerosis and correlate with improved prognosis for vascular disease associated events. While many of the atheroprotective effects of HDL are ascribed to the ability to remove cholesterol from the vasculature through th...
journal_title:Current medicinal chemistry
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更新日期:2009-01-01 00:00:00
abstract::Non-small cell lung cancer (NSCLC) remains a fatal disease: the majority of patients are diagnosed as having metastases or advanced inoperable tumors. The activity of chemotherapy in NSCLC patients is low with objective response rarely complete and sustained. Cisplatin-based combinations are considered as the standard...
journal_title:Current medicinal chemistry
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更新日期:2002-04-01 00:00:00