Journal of molecular biochemistry最新文献_第3页

Molecular dynamics simulations through GPU video games technologies. 分子动力学模拟通过GPU视频游戏技术。

Journal of molecular biochemistry Pub Date : 2014-01-01 Epub Date: 2014-06-30

Styliani Loukatou, Louis Papageorgiou, Paraskevas Fakourelis, Arianna Filntisi, Eleftheria Polychronidou, Ioannis Bassis, Vasileios Megalooikonomou, Wojciech Makałowski, Dimitrios Vlachakis, Sophia Kossida

{"title":"Molecular dynamics simulations through GPU video games technologies.","authors":"Styliani Loukatou, Louis Papageorgiou, Paraskevas Fakourelis, Arianna Filntisi, Eleftheria Polychronidou, Ioannis Bassis, Vasileios Megalooikonomou, Wojciech Makałowski, Dimitrios Vlachakis, Sophia Kossida","doi":"","DOIUrl":"","url":null,"abstract":"Bioinformatics is the scientific field that focuses on the application of computer technology to the management of biological information. Over the years, bioinformatics applications have been used to store, process and integrate biological and genetic information, using a wide range of methodologies. One of the most de novo techniques used to understand the physical movements of atoms and molecules is molecular dynamics (MD). MD is an in silico method to simulate the physical motions of atoms and molecules under certain conditions. This has become a state strategic technique and now plays a key role in many areas of exact sciences, such as chemistry, biology, physics and medicine. Due to their complexity, MD calculations could require enormous amounts of computer memory and time and therefore their execution has been a big problem. Despite the huge computational cost, molecular dynamics have been implemented using traditional computers with a central memory unit (CPU). A graphics processing unit (GPU) computing technology was first designed with the goal to improve video games, by rapidly creating and displaying images in a frame buffer such as screens. The hybrid GPU-CPU implementation, combined with parallel computing is a novel technology to perform a wide range of calculations. GPUs have been proposed and used to accelerate many scientific computations including MD simulations. Herein, we describe the new methodologies developed initially as video games and how they are now applied in MD simulations.","PeriodicalId":73836,"journal":{"name":"Journal of molecular biochemistry","volume":"3 2","pages":"64-71"},"PeriodicalIF":0.0,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4980074/pdf/nihms808031.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34308737","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Ebola virus epidemic: a deliberate accident? 埃博拉病毒流行:蓄意事故?

Journal of molecular biochemistry Pub Date : 2014-01-01

Styliani Loukatou, Paraskevas Fakourelis, Louis Papageorgiou, Vasileios Megalooikonomou, Sophia Kossida, Dimitrios Vlachakis

引用次数: 0

Motifs within the CA-repeat-rich region of Surfactant Protein B (SFTPB) intron 4 differentially affect mRNA splicing. 表面活性剂蛋白B (SFTPB)内含子4 CA-repeat-rich区域内的基序对mRNA剪接的影响存在差异。

Journal of molecular biochemistry Pub Date : 2013-02-20

Wenjun Yang, Lan Ni, Patricia Silveyra, Guirong Wang, Georgios T Noutsios, Anamika Singh, Susan L Diangelo, Olabisi Sanusi, Manmeet Raval, Joanna Floros

{"title":"Motifs within the CA-repeat-rich region of Surfactant Protein B (SFTPB) intron 4 differentially affect mRNA splicing.","authors":"Wenjun Yang, Lan Ni, Patricia Silveyra, Guirong Wang, Georgios T Noutsios, Anamika Singh, Susan L Diangelo, Olabisi Sanusi, Manmeet Raval, Joanna Floros","doi":"","DOIUrl":"","url":null,"abstract":"The first half of the surfactant protein B (SP-B) gene intron 4 is a CA-repeat-rich region that contains 11 motifs. To study the role of this region on SP-B mRNA splicing, minigenes were generated by systematic removal of motifs from either the 5' or 3' end. These were transfected in CHO cells to study their splicing efficiency. The latter was determined as the ratio of completely to incompletely spliced SP-B RNA. Our results indicate that SP-B intron 4 motifs differentially affect splicing. Motifs 8 and 9 significantly enhanced and reduced splicing of intron 4, respectively. RNA mobility shift assays performed with a Motif 8 sequence that contains a CAUC cis-element and cell extracts resulted in a RNA:protein shift that was lost upon mutation of the element. Furthermore, in silico analysis of mRNA secondary structure stability for minigenes with and without motif 8 indicated a correlation between mRNA stability and splicing ratio. We conclude that differential loss of specific intron 4 motifs results in one or more of the following: a) altered splicing, b) differences in RNA stability and c) changes in secondary structure. These, in turn, may affect SP-B content in lung health or disease.","PeriodicalId":73836,"journal":{"name":"Journal of molecular biochemistry","volume":"2 1","pages":"40-55"},"PeriodicalIF":0.0,"publicationDate":"2013-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3656664/pdf/nihms455181.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31442063","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

STAT3 Inhibition Induces Apoptosis in Cancer Cells Independent of STAT1 or STAT2. STAT3抑制诱导独立于STAT1或STAT2的癌细胞凋亡

Journal of molecular biochemistry Pub Date : 2013-02-20

Adetola Shodeinde, Kalyani Ginjupalli, H Dan Lewis, Sheraz Riaz, Beverly E Barton

{"title":"STAT3 Inhibition Induces Apoptosis in Cancer Cells Independent of STAT1 or STAT2.","authors":"Adetola Shodeinde, Kalyani Ginjupalli, H Dan Lewis, Sheraz Riaz, Beverly E Barton","doi":"","DOIUrl":"","url":null,"abstract":"Signal transducers and activators of transcription (STATs) were originally discovered as mediators of signal transduction. Persistent aberrant activation of STAT3 is part of the malignant phenotype of hormone-refractory prostate cancer and pancreatic cancer; this is thought to be mediated by homodimers of phosphorylated STAT3, which translocate to the nucleus. One consequence of persistently-activated STAT3 in malignant cells is that they depend upon it for survival. STAT3 is observed to heterodimerize with STAT1 and STAT2; however the contributions of STAT3:STAT1 and STAT3:STAT2 heterodimers to the survival of malignant cells have not been investigated in detail. Previously we reported that single-stranded oligonucleotides containing consensus STAT3 binding sequences (13410 and 13411) were more effective for inducing apoptosis in prostate cancer cells than antisense STAT3 oligonucleotides. Control oligonucleotides (scrambled sequences) had no effect. STAT3-inhibiting oligonucleotide 13410, but not scrambled-sequence oligonucleotides, induced apoptosis in pancreatic cancer cells as well. Here we report that 13410 and derivative olignucleotides induced apoptosis in STAT1-null and STAT2-null fibrosarcoma cell lines U3A and U6A, as well as in the parental fibrosarcoma cell line 2fTGH. The cell lines expressed constitutively-activated STAT3 and depended on its activity for survival. Forty-eight hr after transfection of 13410 or related oligonucleotides, significant apoptosis was observed in 2fTGH, U3A and U6A cells. Scrambled-sequence oligonucleotides had no effect on survival. These data indicate that neither STAT1 nor STAT2 play significant roles in the maintenance of these cells, and by extension that STAT3:STAT1 and STAT3:STAT2 heterodimers regulate a different set of genes from STAT3:STAT3 homodimers.","PeriodicalId":73836,"journal":{"name":"Journal of molecular biochemistry","volume":"2 1","pages":"18-26"},"PeriodicalIF":0.0,"publicationDate":"2013-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4215738/pdf/nihms-557610.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32786831","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Molecular mechanism-based model to enhance outcomes of dietary intervention studies for disease prevention. 基于分子机制的模型提高疾病预防饮食干预研究的结果。

Journal of molecular biochemistry Pub Date : 2012-10-16

Moul Dey

引用次数: 0

Probing the GnRH receptor agonist binding site identifies methylated triptorelin as a new anti-proliferative agent. 探测GnRH受体激动剂结合位点鉴定甲基化雷公藤雷素作为一种新的抗增殖剂。

Journal of molecular biochemistry Pub Date : 2012-06-16

Kevin Morgan, Samuel P Leighton, Robert P Millar

{"title":"Probing the GnRH receptor agonist binding site identifies methylated triptorelin as a new anti-proliferative agent.","authors":"Kevin Morgan, Samuel P Leighton, Robert P Millar","doi":"","DOIUrl":"","url":null,"abstract":"D-amino acid substitutions at glycine postion 6 in GnRH-I decapeptide can possess super-agonist activity and enhanced in vivo pharmacokinetics. Agonists elicit growth-inhibition in tumorigenic cells expressing the GnRH receptor above threshold levels. However, new agonists with modified properties are required to improve the anti-proliferative range. Effects of residue substitutions and methylations on tumourigenic HEK293[SCL60] and WPE-1-NB26-3 prostate cells expressing the rat GnRH receptor were compared. Peptides were ranked according to receptor binding affinity, induction of inositol phosphate production and cell growth-inhibition. Analogues possessing D-Trp6 (including triptorelin), D-Leu6 (including leuprolide), D-Ala6, D-Lys6, or D-Arg6 exhibited agonist and anti-proliferative activity. Residues His5 or His5,Trp7,Tyr8, corresponding to residues found in GnRH-II, were tolerated, with retention of sub-nanomolar/low nanomolar binding affinities and EC50s for receptor activation and IC50s for cell growth-inhibition. His5D-Arg6-GnRH-I exhibited reduced binding affinity and potency, effective in the mid-nanomolar range. However, all GnRH-II-like analogues were less potent than triptorelin. By comparison, three methylated-Trp6 triptorelin variants showed differential binding, receptor activation and anti-proliferation potency. Significantly, 5-Methyl-DL-Trp6-Triptorelin was equipotent to triptorelin. Subsequent studies should determine whether pharmacologically enhanced derivatives of triptorelin can be developed by further alkylations, without substitutions or cleavable cytotoxic adducts, to improve the extent of growth-inhibition of tumour cells expressing the GnRH receptor.","PeriodicalId":73836,"journal":{"name":"Journal of molecular biochemistry","volume":"1 2","pages":"86-98"},"PeriodicalIF":0.0,"publicationDate":"2012-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3906704/pdf/emss-56340.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32085933","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Therapeutic efficacy of an oncolytic adenovirus containing RGD ligand in minor capsid protein IX and Fiber, Δ24DoubleRGD, in an ovarian cancer model. 含RGD配体的小衣壳蛋白IX和纤维Δ24DoubleRGD溶瘤腺病毒在卵巢癌模型中的治疗效果

Journal of molecular biochemistry Pub Date : 2012-02-15

Lena J Gamble, Hideyo Ugai, Minghui Wang, Anton V Borovjagin, Qiana L Matthews

{"title":"Therapeutic efficacy of an oncolytic adenovirus containing RGD ligand in minor capsid protein IX and Fiber, Δ24DoubleRGD, in an ovarian cancer model.","authors":"Lena J Gamble, Hideyo Ugai, Minghui Wang, Anton V Borovjagin, Qiana L Matthews","doi":"","DOIUrl":"","url":null,"abstract":"Ovarian cancer is the leading cause of gynecological disease death despite advances in medicine. Therefore, novel strategies are required for ovarian cancer therapy. Conditionally replicative adenoviruses (CRAds), genetically modified as anti-cancer therapeutics, are one of the most attractive candidate agents for cancer therapy. However, a paucity of coxsackie B virus and adenovirus receptor (CAR) expression on the surface of ovarian cancer cells has impeded treatment of ovarian cancer using this approach. This study sought to engineer a CRAd with enhanced oncolytic ability in ovarian cancer cells, \"Δ24DoubleRGD.\" Δ24DoubleRGD carries an arginine-glycine-aspartate (RGD) motif incorporated into both fiber and capsid protein IX (pIX) and its oncolytic efficacy was evaluated in ovarian cancer. In vitro analysis of cell viability showed that infection of ovarian cancer cells with Δ24DoubleRGD leads to increased cell killing relative to the control CRAds. Data from this study suggested that not only an increase in number of RGD motifs on the CRAd capsid, but also a change in the repertoir of targeted integrins could lead to enhanced oncolytic potency of Δ24DoubleRGD in ovarian cancer cells in vitro. In an intraperitoneal model of ovarian cancer, mice injected with Δ24DoubleRGD showed, however, a similar survival rate as mice treated with control CRAds.","PeriodicalId":73836,"journal":{"name":"Journal of molecular biochemistry","volume":"1 1","pages":"26-39"},"PeriodicalIF":0.0,"publicationDate":"2012-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3755628/pdf/nihms466707.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31700785","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

N²-Phenyl-9-(hydroxyalkyl)guanines and related compounds are substrates for Herpes simplex virus thymidine kinases. n2 -苯基-9-(羟基烷基)鸟嘌呤及其相关化合物是单纯疱疹病毒胸苷激酶的底物。

Journal of molecular biochemistry Pub Date : 2012-01-01

Andrea Lossani, Lida Savi, Andrzej Manikowski, Andrew Maioli, Joseph Gambino, Federico Focher, Silvio Spadari, George E Wright

{"title":"N2-Phenyl-9-(hydroxyalkyl)guanines and related compounds are substrates for Herpes simplex virus thymidine kinases.","authors":"Andrea Lossani, Lida Savi, Andrzej Manikowski, Andrew Maioli, Joseph Gambino, Federico Focher, Silvio Spadari, George E Wright","doi":"","DOIUrl":"","url":null,"abstract":"Herpes simplex virus (HSV) types 1 and 2 thymidine kinases (TK) are responsible for phosphorylation of antiherpes acyclonucleosides such as acyclovir (ACV) and 9-(4-hydroxybutyl)guanine (HBG). Related compounds, the N2-phenyl-9-(hydroxyalkyl)guanines, are devoid of direct antiviral activity, but potently inhibit the viral TKs and block viral reactivation from latency in vivo. The similarity in structure between the acyclonucleosides and TK inhibitors raised the question of the relevance of phosphorylation of certain of the latter analogs in their mechanisms of action. Using recombinant TKs and HPLC analysis of reaction mixtures, we report that the lead TK inhibitor N2-phenyl-9 -(4-hydroxybutyl)guanine (HBPG) and its pentyl homolog (HPnPG) are excellent substrates for the enzymes, approaching the efficiency with which the natural substrate thymidine is phosphorylated, and significantly better than ACV or HBG. Other 9-hydroxyalkyl congeners are substrates for the enzymes, but with much poorer efficiency. HBPG triphosphate was a poor inhibitor of HSV DNA polymerase, the target of acyclonucleoside triphosphates, suggesting that phosphorylation of HBPG is not important in its mechanism of blocking viral reactivation in vivo. The fact that HBPG is an efficient substrate is consistent, however, with its binding mode based both on molecular modeling studies and x-ray structure of the HBPG:TK complex.","PeriodicalId":73836,"journal":{"name":"Journal of molecular biochemistry","volume":"1 1","pages":"21-25"},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3984574/pdf/nihms556676.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32264606","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0