Proceedings of MOL2NET 2018, International Conference on Multidisciplinary Sciences, 4th edition最新文献

{"title":"Structural insight on the Hsp90-binding modes of Naphthoquinone derivatives. Molecular Modeling study for antitumoral drug design","authors":"Claudio Godoy-Castillo, Jorge González, J. Soto-Delgado","doi":"10.3390/MOL2NET-04-06099","DOIUrl":"https://doi.org/10.3390/MOL2NET-04-06099","url":null,"abstract":"Heat shock proteins (HSPs) constitute a large family of proteins involved in protein folding and maturation whose expression is induced by heat shock or other stressors. HSPs play important roles in carcinogenesis via the regulation of angiogenesis, cell proliferation, migration, invasion, and metastasis. One of the most attractive targets for novel antitumor agents during recent years is the Heat shock proteins 90 (Hsp90), which is an essential molecular chaperone and it is responsible for the folding and maturation of nascent proteins.1 In this context, inhibition of Hsp90 has potential to disrupt multiple oncogenic pathways by an indirect attack on critical proteins and has become an attractive target for cancer therapy.2 This work aims to develop of new molecules based on quinone scaffold due that quinones derivatives have demonstrated potent anti-proliferative activity against estrogen-dependent cancers cell, as well as, induce the degradation of oncogenic Hsp90 client proteins. The set of 35 molecules reported by Blagg et al.3 were studied based in a hybrid strategy including Molecular Docking, Molecular Dynamics and 3D-QSAR analysis to identify the most relevant ligand-receptor interactions.4 The Correlation between the free energy of binding and binding modes for nafthoquinones derivatives are discussed. These results provide a new insight into protein–ligand interactions into the Hsp90, in addition, the analysis of the contour maps derived for 3D-QSAR provide helpful way about the rational modification of molecules in order to design more potent Hsp90 inhibitors.","PeriodicalId":20475,"journal":{"name":"Proceedings of MOL2NET 2018, International Conference on Multidisciplinary Sciences, 4th edition","volume":"48 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85453007","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Utilisation of click chemistry in medicinal chemistry. Applications to the synthesis of new bioactive triarylmethanes.","authors":"Ameni Hadj Mohamed, M. E. Arbi, Moncef Msaddek, M. S. Veitía","doi":"10.3390/MOL2NET-04-06100","DOIUrl":"https://doi.org/10.3390/MOL2NET-04-06100","url":null,"abstract":"","PeriodicalId":20475,"journal":{"name":"Proceedings of MOL2NET 2018, International Conference on Multidisciplinary Sciences, 4th edition","volume":"19 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75067175","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Imbalance Glutathione Biosynthesis in ASD: A kinetic patterns “in vivo”","authors":"Carmen Jiménez Espinoza, Francisco Marcano Serrano, J. González-Mora","doi":"10.3390/MOL2NET-04-06098","DOIUrl":"https://doi.org/10.3390/MOL2NET-04-06098","url":null,"abstract":"Glutathione (GSH; γ-L-glutamyl-L-cysteinyl-glycine) is the most abundant endogenous antioxidant present in mammalian cells (0.1 to 15 mM) and plays a protective role for exogenous toxins and endogenous, especially in the central nervous system. Biochemistly knowns that biosynthesis pathway have two consecutive reactions that consume ATP, including two enzymes; glutamate cysteine ligase (GCL), [E-6.3.2.2], formerly known as ganma-glutamylcysteine synthetase (GCS) and glutathione synthetase (GSS), [E-6.3 .2.3] to generate GSH. The defense against the toxic effects of reactive oxygen species (ROS) is an essential task within the brain during a long human life, which indicates the presence of an effective antioxidant system. However, the balance between ROS generation and antioxidant processes can be altered, causing neurological disorders such as Alzheimer's and Parkinson's. The same way, markers of oxidative stress are strongly associated with severe mitochondrial dysfunction in autism pathology. Previous studies indicate that ASD is associated with deficits in the antioxidant defense of glutathione in selective regions of the brain, however, the molecular mechanisms of oxidative stress continue being unclear. In our previous studies we described the kinetic imbalance in tri-cellular metabolism of N-acetyl-aspartyl glutamate (NAAG), in anterior (ACC) and posterior (PCC) cingulated cortices relate to the executive control networks and the attention alert functions respectively, linked to ASD pathogenesis. In the present study, we use resonance magnetic spectroscopy (1H-MRS) to study the specie reduced of glutathione (GSH) biosynthesis in the cingulated cortices, as target of oxidative stress in individuals with ASD. The single voxel of 1H-MRS in bilateral anterior (ACC) and posterior (PCC) cingulated cortices, in adults with ASD and controls with typical development (n = 21 and n = 46 respectively) were assessed. Glutathione (GSH) concentration were significantly decreased in ACC (P = 0.05). The affinity between enzyme and substrate associated with the biosynthesis of reduced species at glutathione was calculate by Michaelis Menten constant (Km) showing that glutathione biosynthesis decreased significant (1.1e-12 mM; R2 = 0.001) in anterior cingulate cortex in autism and, the dissociation constant (ki) was reduced by 67.22% in consequence. On the other hand, maximum rate (Vmax) of the appearance of the product, which depends on the slowest pathway of the enzymatic reaction was significantly decreased (15.12 µM / min; R2 = 0.51) in PCC. Our findings indicate that, with a small amount of substrate, the rate increases rapidly and linearly in ACC, suggesting that the active sites of the enzyme are saturated with the substrate, whereas the enzyme-substrate complex is very tight and rarely dissociates without the substrate reacting to give the product. Imbalance enzymatic kinetic in glutathione biosynthesis in the autism cingulated cortices is a novel fin","PeriodicalId":20475,"journal":{"name":"Proceedings of MOL2NET 2018, International Conference on Multidisciplinary Sciences, 4th edition","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82367676","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Computational campaign to discover novel human 20S proteasome inhibitors","authors":"P. Fernandes, Romina A. Guedes, Bruno L. Victor, R. Guedes","doi":"10.3390/MOL2NET-04-06097","DOIUrl":"https://doi.org/10.3390/MOL2NET-04-06097","url":null,"abstract":".","PeriodicalId":20475,"journal":{"name":"Proceedings of MOL2NET 2018, International Conference on Multidisciplinary Sciences, 4th edition","volume":"107 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75668293","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"EVOLUTIONARY VARIATIONS IN HLH DOMAIN MODULATES THE FAST INACTIVATION PHASE IN CALCIUM SELECTIVE TRP CHANNELS.","authors":"S. Brauchi, Lisandra Flores, Kattina Zavala, J. Opazo, Daniel Bustos, W. González","doi":"10.3390/MOL2NET-04-06096","DOIUrl":"https://doi.org/10.3390/MOL2NET-04-06096","url":null,"abstract":"","PeriodicalId":20475,"journal":{"name":"Proceedings of MOL2NET 2018, International Conference on Multidisciplinary Sciences, 4th edition","volume":"18 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74473655","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of bacteria of aquatic origin as fish probiotic in vitro","authors":"Mouna Jlidi, A. Akremi, Adel Haj Brahim, Houda Hmani, L. Daoud, M. Ali, N. Souissi, S. Bejar, Mamdouh Ben Ali","doi":"10.3390/MOL2NET-04-06095","DOIUrl":"https://doi.org/10.3390/MOL2NET-04-06095","url":null,"abstract":": The rapid development of aquaculture, its intensification, and the occurrence of fish health problems on farms push to develop alternative methods to antibiotics and chemotherapy for controlling fish diseases. Probiotics may provide a potential alternative method to protect fish from opportunistic and pathologic bacteria and promote a balanced environment. In this work, we have assessed the in vitro probiotic properties of twenty one bacteria from aquatic and fish origin, for their application in aquaculture. Selection was based on their antimicrobial activity (Bacteriocin) against fish pathogens and their in vitro safety assessment. This includes the evaluation of their haemolytic, proteolytic and mucinolytic activities, bile salt deconjugation ability and antibiotic susceptibility. Twelve of the twenty one bacteria isolated from several showed strong antibacterial activity against several pathogenic species such as Lactococcus garvieae , Vibrio anguillarum , Vibrio harveyi , Aeromonas hydrophila and Aeromonas salmonicida , and were taxonomically identified by partial 16S rDNA gene sequencing. The cell-free culture supernatants from cultures of these twelve strains were treated with proteinase K (10 mg/ml; 37ºC, 1h) and submitted to heat treatment (100ºC, 10 min), which showed that eleven strains exert extracellular antimicrobial activity against fish pathogens due to the production and secretion of thermo-stable antimicrobial peptides (i.e., Bacteriocins). The tested strains showed a great heterogeneity respect to their safety and antibiotic susceptibility.","PeriodicalId":20475,"journal":{"name":"Proceedings of MOL2NET 2018, International Conference on Multidisciplinary Sciences, 4th edition","volume":"37 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76588553","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Accelerating the DszD enzyme for the Biodesulfurization of Crude Oil and Derivatives","authors":"M. Ramos, P. Ferreira, S. Sousa, P. Fernandes","doi":"10.3390/MOL2NET-04-06087","DOIUrl":"https://doi.org/10.3390/MOL2NET-04-06087","url":null,"abstract":"It is known that fossil fuel combustion is one of the main environmental problems of the modern era, and the sulfur content of crude oil [1] contributes heavily to this. One of the main sulphurous compounds present in crude oil is dibenzothiophene (DBT). Due to its harmfulness, several governments around the world have been imposing stricter restrictions regarding the sulfur content in fossil fuels. The desulfurization of crude oil is currently carried out using costly chemical processes. One alternative to these costly chemical processes involves the use of specific microorganisms, such as Rhodococcus erythropolis, capable of utilizing DBT as a sole source of sulfur. The process carried out by R. erytrhopolis is called the 4S pathway and is conducted by the action of four enzymes of the dibenzothiophene desulfurization enzymes (dsz) family. DszA, DszB, DszC and DszD. The major limitation of this pathway is the slow catalytic rates of the four enzymes, which limits its application in industry. The enhancement of the catalytic power of enzymes is a subject of enormous interest both for science and for industry. The latter, in particular, due to the vast applications enzymes can have in industrial processes. In this work, we sought to enhance the turnover rate of DszD from Rhodococcus erythropolis, a NADH-FMN oxidoreductase responsible to supply FMNH2 to DszA and DszC in the biodesulfurization process of crude oil, the 4S pathway. For that purpose, we replaced the wild type spectator residue of the rate-limiting step of the reduction of FMN to FMNH2 catalysed by DszD, known to have an important role in its energetic profile, with all the natural occurring amino acids, one at a time, using computational methodologies, and repeated the above-mentioned reaction with each mutant. To calculate the different free energy profiles, one for each mutated model, we applied quantum mechanical methods (namely DFT) within an ONIOM scheme. The free energy barriers obtained for the different mutated models varied between 15.1 kcal.mol-1 and 29.9 kcal.mol-1. Multiple factors contributed to the different ΔGs. The most relevant were electrostatic interactions and the induction of a favourable alignment between substrate and cofactor. These results confirm the great potential that chirurgic mutations have to increase the catalytic power of DszD in relation to the wt enzyme. \u0000 \u0000[1] N. Kamali, M. Tavallaie, B. Bambai, A. A. Karkhane and M. Miri, Biotechnol Lett, 2010, 32, 921-927.","PeriodicalId":20475,"journal":{"name":"Proceedings of MOL2NET 2018, International Conference on Multidisciplinary Sciences, 4th edition","volume":"61 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76413085","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the Catalytic Mechanism of the Malonyl-Acetyl Transferase Domain of Human Fatty Acid Synthase","authors":"P. Fernandes, Pedro Paiva, S. Sousa, M. Ramos","doi":"10.3390/MOL2NET-04-06086","DOIUrl":"https://doi.org/10.3390/MOL2NET-04-06086","url":null,"abstract":"","PeriodicalId":20475,"journal":{"name":"Proceedings of MOL2NET 2018, International Conference on Multidisciplinary Sciences, 4th edition","volume":"29 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85103055","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Combined experimental and computational studies devoted to the synthesis of 1,4-lactones","authors":"Juliana F. Rocha, David S. Freitas, Jennifer Noro, C. Teixeira, Cristina E. A. Sousa, S. Sousa, M. Alves, N. Cerqueira","doi":"10.3390/mol2net-04-06089","DOIUrl":"https://doi.org/10.3390/mol2net-04-06089","url":null,"abstract":"","PeriodicalId":20475,"journal":{"name":"Proceedings of MOL2NET 2018, International Conference on Multidisciplinary Sciences, 4th edition","volume":"10 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89156731","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A proposed new measure to verify the general version of Chargaff 2nd rule.","authors":"Camilo Fuentes Beals, Gonzalo Riadi Mahias, Karen Y. Oróstica, Ignacio Vidal","doi":"10.3390/MOL2NET-04-06090","DOIUrl":"https://doi.org/10.3390/MOL2NET-04-06090","url":null,"abstract":"In the 40’s, Erwin Chargaff was the first to observe the parity between Adenines (A) and Timinies (T) and Citosines (C) and Guanines (G), in the molecule of DNA. In the 60’s, Chargaff found a second parity rule. This time in a single strand of DNA. The amounts of A’s and T’s, and the amounts of C’s and G’s is similar. The explanation of the first rule is the complementary nature of the double stranded helix of the DNA molecule. However, for the 2nd rule, a biological explanation has remained a mystery. In the last 40 years, a generalization of the second rule was proposed, to explain the 2nd rule as a particular case. This generalization states that for any given k-mer and its reverse complement (RC), the number of times both are found is similar in a single strand of DNA. Two measures have been proposed to test the generalized Chargaff’s 2nd rule (gC2r), both include an artifact regarding the length of the genomes. This has led the authors to think there is a minimum length of a genome and a maximum k-mer for compliance. We propose a new way to measure the compliance of any given genome to the gC2r. The measure is the proportion of the genome which complies with gC2r. The compliance is measured per pair of kmer/k-merRC, using the natural logarithm of the number of times the k-mer is found, divided by the number of times its reverse complement is found in the genome or ln(#k-mer/k-merRC). This measure is independent of the size of the analyzed k-mer and the size of the genome. This measure has been implemented in a software, ChargaffCracker, which can rapidly analyze sequences and deliver a statistical report. We have generated random genomes based on the proportions and lengths of biological prokaryote genome sequences and compared them. We conclude hypothesizing that: 1. The compliance of the gC2r is a consequence, not cause of the 2nd rule and; 2. Although Chargaff’s 2nd rule might be a consequence of transpositions and inversions, the limits of compliance of the gC2r is a property of the sequence model of genomes, not of the biology of organisms. However, this property might have been selected to fulfill biological needs in genome evolution.","PeriodicalId":20475,"journal":{"name":"Proceedings of MOL2NET 2018, International Conference on Multidisciplinary Sciences, 4th edition","volume":"7 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88651227","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}