Abstract:
:Free energy simulations are a powerful tool to study molecular recognition. The most rigorous variants can provide in depth understanding for a particular system, but are not suited for high throughput application to large libraries of compounds. Related, but less expensive methods are increasingly popular, including continuum electrostatic methods like PBSA ("Poisson-Boltzmann Surface Area") and Linear Response or Linear Interaction Energy methods (LRA, LIE). Here, we review the theoretical background of these methods and provide a unified framework. We focus on the electrostatic contributions to the binding free energy, analyzing nonpolar contributions more briefly. The methods reviewed introduce a multi-step pathway for ligand unbinding, with distinct steps that uncharge the bound ligand, then recharge the unbound ligand. They assume that the system responds to the charging/uncharging in a linear way. With this approximation, the free energy can be described by its one or two first derivatives with respect to a progress variable. The methods can then be classified according to which states of the system are actually simulated and the number of free energy derivatives (one or two) that are employed. The analysis should help clarify the relations between several important free energy methods and the approximations they make. It can suggest new ways to test them, and provide routes for their improvement.
journal_name
Curr Pharm Desjournal_title
Current pharmaceutical designauthors
Simonson Tdoi
10.2174/1381612811319230008subject
Has Abstractpub_date
2013-01-01 00:00:00pages
4241-56issue
23eissn
1381-6128issn
1873-4286pii
CPD-EPUB-20121120-11journal_volume
19pub_type
杂志文章,评审abstract:BACKGROUND:Type 2 diabetes mellitus (DM) is associated with a considerable risk of cardiovascular and renal disease, including heart failure. Sodium-glucose cotransporter 2 (SGLT2) inhibitors have demonstrated unprecedented cardiorenal protective effects in large scale clinical trials of patients with or without diabet...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/1381612826666201103122813
更新日期:2020-11-03 00:00:00
abstract::The performance- and alertness-sustaining/restoring effects of modafinil during sleep deprivation in normal, healthy adults were reviewed. Results indicate that modafinil is efficacious for sustaining/restoring objective performance and alertness during sleep deprivation with few adverse effects. At appropriate dosage...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161206777698819
更新日期:2006-01-01 00:00:00
abstract::The present review discusses the mechanism of late stent thrombosis and its distinction from restenosis and summarizes the advisory note issued by FDA on the proper usage of different treatments available for atherosclerosis. In light of the latest developments, a plethora of new stents have been and continue to be de...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161208785294573
更新日期:2008-01-01 00:00:00
abstract::Mitochondria are involved in different physiological and pathological processes that are crucial for tumor cell physiology, growth and survival. Since cancer cells have frequently disrupted different cell death pathways that promote their survival, mitochondria may be key organelles to promote cell death in cancer cel...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161211796904803
更新日期:2011-01-01 00:00:00
abstract::Periodontal disease is chronic inflammation of periodontal tissues resulting in formation of periodontal pockets, periodontal attachment loss and progressive destruction of the ligament and alveolar bone. This review gives an update on periodontal disease pathogenesis, which is important for the development of novel m...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612821666150531171829
更新日期:2015-01-01 00:00:00
abstract::Ras is a 21 kDa membrane-localized G protein that is coupled to receptor and non-receptor tyrosine kinase activation of downstream cytoplasmic and nuclear events. Mutated ras genes are common, and occur in a wide variety of human malignancies. These activating mutations result in constitutive signaling, thereby stimul...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612013397258
更新日期:2001-11-01 00:00:00
abstract:BACKGROUND:New Oral Anticoagulants (NOACs) are effective and widely used to prevent and treat thromboembolic diseases, but the response to NOACs differs according to ABCB1 genotypes. OBJECTIVE:We investigated the effects of ABCB1 genotypes on the pharmacokinetics and clinical outcomes of NOACs. METHODS:We searched Pu...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,meta分析,评审
doi:10.2174/1381612824666181018153641
更新日期:2018-01-01 00:00:00
abstract:BACKGROUND:The population with autism spectrum disorder (ASD) has been increasing and is currently estimated to be 1 in 58 births. The increased prevalence of ASD together with the lack of knowledge on the processes of aging in this population, the support needed at this stage of life, and the associated risk factors, ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612825666191204165117
更新日期:2019-01-01 00:00:00
abstract::Since identifying a transmissible agent responsible for tumorigenesis in chickens, the v-Src oncogene, significant progress has been made in determining the functions of its cellular homologue. c-Src is the product of the SRC gene and has been found both over-expressed and highly activated in a number of human cancers...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612053507576
更新日期:2005-01-01 00:00:00
abstract::The phenomenon of blood serum atherogenicity was described as the ability of human serum to induce lipid accumulation in cultured cells. The results of recent two-year prospective study in asymptomatic men provided the evidence for association between the changes in serum atherogenicity and dynamics of carotid intima-...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/1381612820666140212194614
更新日期:2014-01-01 00:00:00
abstract::The brain is a complex, regulated organ with a highly controlled access mechanism: The Blood-Brain Barrier (BBB). The selectivity of this barrier is a double-edged sword, being both its greatest strength and weakness. This weakness is evident when trying to target therapeutics against diseases within the brain. Diseas...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/1381612824666171201115126
更新日期:2018-01-01 00:00:00
abstract::We illustrate the use of quantitative proteomics, namely isotope-coded affinity tag labelling and tandem mass spectrometry, to assess the targets and effects of the blockade of matrix metalloproteinases by an inhibitor drug in a breast cancer cell culture system. Treatment of MT1-MMP-transfected MDA-MB-231 cells with ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161207779313524
更新日期:2007-01-01 00:00:00
abstract::Integrins alpha(1)beta(1) and alpha(2)beta(1) are highly expressed on the microvascular endothelial cells, and blocking of their adhesive properties significantly reduced the VEGF-driven neovascularization ratio and tumor growth in animal models. Hence, inhibitors of the alpha(1)beta(1) and alpha(2) beta(1) integrins,...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161207782023766
更新日期:2007-01-01 00:00:00
abstract::Angiogenic eye disease is among the most common causes of blindness worldwide. Current treatment approaches are insufficiently effective and partially associated with significant adverse effects. From an investigational view, the eye provides an ideal setting to observe real-time and serial observations of angiogenesi...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612054367292
更新日期:2005-01-01 00:00:00
abstract::We estimated the frequency of detection of different human papillomavirus (HPV) types in women with atypical squamous cells of undetermined significance (ASCUS) or low-grade squamous intraepithelial lesion (LSIL) cytology in a population-based primary screening programme. 247 liquid-based cytology (LBC) samples with A...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:
更新日期:2013-01-01 00:00:00
abstract::Nitric oxide is a ubiquitous molecule involved in a variety of biological processes. The specific action of NO depends on its enzymatic sources namely neuronal nitric oxide synthase (nNOS), endothelial NOS (eNOS) and inducible NOS (iNOS) and all three isoforms have been localized in the gastrointestinal tract. Constit...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612013398491
更新日期:2001-01-01 00:00:00
abstract::Schizophrenia is a complex pathology characterized by the occurrence of a variety of symptoms classified as positive, negative and cognitive. Although the exact etiopathogenesis of this disorder has not been unraveled yet, many theories have been endorsed during the last years. Among these, the neurochemical theories ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612821666150105122422
更新日期:2015-01-01 00:00:00
abstract:OBJECTIVES:To investigate if low-dose lithium may counteract the microstructural and metabolic brain changes proposed to occur in individuals at ultra-high risk (UHR) for psychosis. METHODS:Hippocampal T2 relaxation time (HT2RT) and proton magnetic resonance spectroscopy ((1)H-MRS) measurements were performed prior to...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/138161212799316163
更新日期:2012-01-01 00:00:00
abstract::Nanogels are nanosized hydrogel particles formed by physical or chemical cross-linked polymer networks. The advantageous properties of nanogels related to the ability of retaining considerable amount of water, the biocompatibility of the polymers used, the ability to encapsulate and protect a large quantity of payload...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161281941131219124142
更新日期:2013-01-01 00:00:00
abstract::Hereditary hemorrhagic telangiectasia (HHT) is characterized by vessel alterations such as dilatation of postcapillary venules and arterio-venous communications, which account for the major clinical manifestations of the disease. Two types of HHT have been characterized HHT-1 and HHT-2, respectively, depending the for...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161206776361228
更新日期:2006-01-01 00:00:00
abstract::In recent years several new drugs (oxcarbazepine, lamotrigine, topiramate, gabapentin, zonisamide, tiagabine, fosphenytoin, vigabatrin and felbamate) have been added to the therapeutic armamentarium against epilepsy. Some of these represent structural modifications of pre-existing compounds, others were developed with...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612003400245
更新日期:2000-05-01 00:00:00
abstract::The serotonergic system is involved in pathomechanisms of both epilepsy and neuropathic pain. So far, participation in the epileptogenesis and maintenance of epilepsy was proved for 5-HT1A, 5-HT2C, 5-HT3, 5-HT4 and 5-HT7 receptors as well as 5-HTT serotonin transporter. Depending on the receptor type or its localizati...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612821666141121114917
更新日期:2015-01-01 00:00:00
abstract::Mass spectrometry information has long offered the potential of discovering biomarkers that would enable clinicians to diagnose disease, and treat it with targeted therapies. PeptideAtlas currently provides access to large-scale spectra data and identification information. This data, and the generation of targeted pep...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/138161212799277833
更新日期:2012-01-01 00:00:00
abstract::Nonalcoholic fatty liver disease (NAFLD) affects about 20%-30% of the general population, and its clinical relevance arises from the fact that 20%-30% of these subjects develop non-alcoholic steatohepatitis (NASH), a condition at risk of cirrhosis progression. In addition NAFLD, and in particular NASH patients, are al...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:
更新日期:2013-01-01 00:00:00
abstract:BACKGROUND:Heat shock proteins are powerful endogenous cytoprotective proteins which help cells to survive recurrent cellular stress events. Identifying the underlying molecular mechanisms and molecular targets is especially interesting since it may help to develop new therapeutic strategies for the treatment of diseas...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612822666160519113339
更新日期:2016-01-01 00:00:00
abstract:BACKGROUND:Ulinastatin (UTI) plays the beneficial roles in modifying cerebral ischemic injury evoked by cardiac arrest (CA). XueBiJing (XBJ), comprised of extracts from Chinese herbals, has been used for the treatment of sepsis and ischemic disorders linked to multiple organ dysfunction syndromes. The current study was...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/1381612825666190206224134
更新日期:2018-01-01 00:00:00
abstract::Today, in spite of being older than a century (born in 1911), the Pictet-Spengler two component reaction (PS-2CR) is still one of the most popular reactions, not only for the synthesis of tetrahydroisoquinolines (THIQs), tetrahydro-β-carbolines (THBCs), or more complex structures containing these two privileged moieti...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612822666151231100247
更新日期:2016-01-01 00:00:00
abstract::Catheter ablation for rhythm control in atrial fibrillation has been recognized as an established treatment. Patients with atrial fibrillation suffer from an increased risk of thromboembolic events. Long-term stroke risk and mortality have been shown to be reduced after catheter ablation, still the procedure per se is...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612822666161205115101
更新日期:2017-01-01 00:00:00
abstract::A new controlled delivery system has been developed for ropinirole (RP) for the treatment of Parkinson´s Disease (PD) consisting in PLGA microparticles (MPs) which exhibited in vitro constant release of RP (78.23 µg/day/10 mg MPs) for 19 days. The neuroprotective effects of RP released from MPs were evaluated in SKN-A...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/1381612822666160928145346
更新日期:2017-01-01 00:00:00
abstract::LIM (Lin-11, Isl-1, Mec-3), RING (Really interesting new gene), PHD (Plant homology domain) and MYND (myeloid, Nervy, DEAF-1) domains are all zinc-binding domains that ligate two zinc ions. Unlike the better known classical zinc fingers, these domains do not bind DNA, but instead mediate interactions with other protei...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161209789271861
更新日期:2009-01-01 00:00:00