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Correlation and prediction of gene expression level from amino acid and dipeptide composition of its protein
Gajendra PS Raghava, Joon H Han
BMC Bioinformatics , 2005, DOI: 10.1186/1471-2105-6-59
Abstract: We compute the correlation between expression of a gene and amino acid composition of its protein. It was observed that some residues (like Ala, Gly, Arg and Val) have significant positive correlation (r > 0.20) and some other residues (Like Asp, Leu, Asn and Ser) have negative correlation (r < -0.15) with the expression of genes. A significant negative correlation (r = -0.18) was also found between length and gene expression. These observations indicate the relationship between percent composition and gene expression level. Thus, attempts have been made to develop a Support Vector Machine (SVM) based method for predicting the expression level of genes from its protein sequence. In this method the SVM is trained with proteins whose gene expression data is known in a given condition. Then trained SVM is used to predict the gene expression of other proteins of the same organism in the same condition. A correlation coefficient r = 0.70 was obtained between predicted and experimentally determined expression of genes, which improves from r = 0.70 to 0.72 when dipeptide composition was used instead of residue composition. The method was evaluated using 5-fold cross validation test. We also demonstrate that amino acid composition information along with gene expression data can be used for improving the function classification of proteins.There is a correlation between gene expression and amino acid composition that can be used to predict the expression level of genes up to a certain extent. A web server based on the above strategy has been developed for calculating the correlation between amino acid composition and gene expression and prediction of expression level http://kiwi.postech.ac.kr/raghava/lgepred/ webcite. This server will allow users to study the evolution from expression data.The use of microarray technologies to monitor gene expression in model organisms, cell lines and tissues has become an important part of biological research over the last several years. Ev
The Feasibility of Enzyme Targeted Activation for Amino Acid/Dipeptide Monoester Prodrugs of Floxuridine; Cathepsin D as a Potential Targeted Enzyme  [PDF]
Yasuhiro Tsume,Gordon L. Amidon
Molecules , 2012, DOI: 10.3390/molecules17043672
Abstract: The improvement of therapeutic efficacy for cancer agents has been a big challenge which includes the increase of tumor selectivity and the reduction of adverse effects at non-tumor sites. In order to achieve those goals, prodrug approaches have been extensively investigated. In this report, the potential activation enzymes for 5¢-amino acid/dipeptide monoester floxuridine prodrugs in pancreatic cancer cells were selected and the feasibility of enzyme specific activation of prodrugs was evaluated. All prodrugs exhibited the range of 3.0–105.7 min of half life in Capan-2 cell homogenate with the presence and the absence of selective enzyme inhibitors. 5¢-O-L-Phenylalanyl-L-tyrosyl-floxuridine exhibited longer half life only with the presence of pepstatin A. Human cathepsin B and D selectively hydrolized 5¢-O-L-phenylalanyl-L-tyrosylfloxuridine and 5¢-O-L-phenylalanyl-L-glycylfloxuridine compared to the other tested prodrugs. The wide range of growth inhibitory effect by floxuridine prodrugs in Capan-2 cells was observed due to the different affinities of prodrug promoieties to enyzmes. In conclusion, it is feasible to design prodrugs which are activated by specific enzymes. Cathepsin D might be a good candidate as a target enzyme for prodrug activation and 5¢-O-L-phenylalanyl-L-tyrosylfloxuridine may be the best candidate among the tested floxuridine prodrugs.
Amino Acid Properties Conserved in Molecular Evolution  [PDF]
Witold R. Rudnicki, Teresa Mroczek, Pawe? Cudek
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0098983
Abstract: That amino acid properties are responsible for the way protein molecules evolve is natural and is also reasonably well supported both by the structure of the genetic code and, to a large extent, by the experimental measures of the amino acid similarity. Nevertheless, there remains a significant gap between observed similarity matrices and their reconstructions from amino acid properties. Therefore, we introduce a simple theoretical model of amino acid similarity matrices, which allows splitting the matrix into two parts – one that depends only on mutabilities of amino acids and another that depends on pairwise similarities between them. Then the new synthetic amino acid properties are derived from the pairwise similarities and used to reconstruct similarity matrices covering a wide range of information entropies. Our model allows us to explain up to 94% of the variability in the BLOSUM family of the amino acids similarity matrices in terms of amino acid properties. The new properties derived from amino acid similarity matrices correlate highly with properties known to be important for molecular evolution such as hydrophobicity, size, shape and charge of amino acids. This result closes the gap in our understanding of the influence of amino acids on evolution at the molecular level. The methods were applied to the single family of similarity matrices used often in general sequence homology searches, but it is general and can be used also for more specific matrices. The new synthetic properties can be used in analyzes of protein sequences in various biological applications.
Investigation of Chiral Molecular Micelles by NMR Spectroscopy and Molecular Dynamics Simulation  [PDF]
Kevin F. Morris, Eugene J. Billiot, Fereshteh H. Billiot, Kenny B. Lipkowitz, William M. Southerland, Yayin Fang
Open Journal of Physical Chemistry (OJPC) , 2012, DOI: 10.4236/ojpc.2012.24032
Abstract: NMR spectroscopy and Molecular Dynamics (MD) simulation analyses of the chiral molecular micelles poly-(Sodium Undecyl-(L,L)-Leucine-Valine) (poly-SULV) and poly-(Sodium Undecyl-(L,L)-Valine-Leucine) (poly-(SUVL)) are reported. Both molecular micelles are used as chiral selectors in electrokinetic chromatography and each consists of covalently linked surfactant chains with chiral dipeptide headgroups. To provide experimental support for the structures from MD simulations, NOESY spectra were used to identify protons in close spatial proximity. Results from the NOESY analyses were then compared to radial distribution functions from MD simulations. In addition, the hydrodynamic radii of both molecular micelles were calculated from NMR-derived diffusion coefficients. Corresponding radii from the MD simulations were found to be in agreement with these experimental results. NMR diffusion experiments were also used to measure association constants for polar and non-polar binaphthyl analytes binding to both molecular micelles. Poly (SUVL) was found to bind the non-polar analyte enantiomers more strongly, while the more polar analyte enantiomers interacted more strongly with poly(SULV). MD simulations in turn showed that poly(SULV) had a more open structure that gave greater access for water molecules to the dipeptide headgroup region.
Molecular Evolution of Plant AAP and LHT Amino Acid Transporters  [PDF]
Mechthild Tegeder,John M. Ward
Frontiers in Plant Science , 2012, DOI: 10.3389/fpls.2012.00021
Abstract: Nitrogen is an essential mineral nutrient and it is often transported within living organisms in its reduced form, as amino acids. Transport of amino acids across cellular membranes requires proteins, and here we report the phylogenetic analysis across taxa of two amino acid transporter families, the amino acid permeases (AAPs) and the lysine–histidine-like transporters (LHTs). We found that the two transporter families form two distinct groups in plants supporting the concept that both are essential. AAP transporters seem to be restricted to land plants. They were found in Selaginella moellendorffii and Physcomitrella patens but not in Chlorophyte, Charophyte, or Rhodophyte algae. AAPs were strongly represented in vascular plants, consistent with their major function in phloem (vascular tissue) loading of amino acids for sink nitrogen supply. LHTs on the other hand appeared prior to land plants. LHTs were not found in chlorophyte algae Chlamydomonas reinhardtii and Volvox carterii. However, the characean alga Klebsormidium flaccidum encodes KfLHT13 and phylogenetic analysis indicates that it is basal to land plant LHTs. This is consistent with the hypothesis that characean algae are ancestral to land plants. LHTs were also found in both S. moellendorffii and P. patens as well as in monocots and eudicots. To date, AAPs and LHTs have mainly been characterized in Arabidopsis (eudicots) and these studies provide clues to the functions of the newly identified homologs.
SCMCRYS: Predicting Protein Crystallization Using an Ensemble Scoring Card Method with Estimating Propensity Scores of P-Collocated Amino Acid Pairs  [PDF]
Phasit Charoenkwan, Watshara Shoombuatong, Hua-Chin Lee, Jeerayut Chaijaruwanich, Hui-Ling Huang, Shinn-Ying Ho
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0072368
Abstract: Existing methods for predicting protein crystallization obtain high accuracy using various types of complemented features and complex ensemble classifiers, such as support vector machine (SVM) and Random Forest classifiers. It is desirable to develop a simple and easily interpretable prediction method with informative sequence features to provide insights into protein crystallization. This study proposes an ensemble method, SCMCRYS, to predict protein crystallization, for which each classifier is built by using a scoring card method (SCM) with estimating propensity scores of p-collocated amino acid (AA) pairs (p = 0 for a dipeptide). The SCM classifier determines the crystallization of a sequence according to a weighted-sum score. The weights are the composition of the p-collocated AA pairs, and the propensity scores of these AA pairs are estimated using a statistic with optimization approach. SCMCRYS predicts the crystallization using a simple voting method from a number of SCM classifiers. The experimental results show that the single SCM classifier utilizing dipeptide composition with accuracy of 73.90% is comparable to the best previously-developed SVM-based classifier, SVM_POLY (74.6%), and our proposed SVM-based classifier utilizing the same dipeptide composition (77.55%). The SCMCRYS method with accuracy of 76.1% is comparable to the state-of-the-art ensemble methods PPCpred (76.8%) and RFCRYS (80.0%), which used the SVM and Random Forest classifiers, respectively. This study also investigates mutagenesis analysis based on SCM and the result reveals the hypothesis that the mutagenesis of surface residues Ala and Cys has large and small probabilities of enhancing protein crystallizability considering the estimated scores of crystallizability and solubility, melting point, molecular weight and conformational entropy of amino acids in a generalized condition. The propensity scores of amino acids and dipeptides for estimating the protein crystallizability can aid biologists in designing mutation of surface residues to enhance protein crystallizability. The source code of SCMCRYS is available at http://iclab.life.nctu.edu.tw/SCMCRYS/.
Extreme genetic code optimality from a molecular dynamics calculation of amino acid polar requirement  [PDF]
Thomas Butler,Nigel Goldenfeld,Damien Mathew,Zaida Luthey-Schulten
Quantitative Biology , 2007,
Abstract: A molecular dynamics calculation of the amino acid polar requirement is presented and used to score the canonical genetic code. Monte Carlo simulation shows that this computational polar requirement has been optimized by the canonical genetic code more than any previously-known measure. These results strongly support the idea that the genetic code evolved from a communal state of life prior to the root of the modern ribosomal tree of life.
Middle Molecular Weight Heparinyl Amino Acid Derivatives (MHADs) Function as Indirect Radical Scavengers in Vitro  [PDF]
Seiichi Takeda, Takao Toda, Kazuki Nakamura
Pharmacology & Pharmacy (PP) , 2016, DOI: 10.4236/pp.2016.73015
Abstract: We conducted the novel synthesis of middle molecular weight heparinyl amino acid derivatives (MHADs) to reduce the adverse effect of heparin (HE) based on its anticoagulant activity. Subsequently, we investigated the radical scavenging effects of 12 kinds of MHAD on cultured human umbilical vein endothelial cells (HUV-ECs) damaged by oxygen free radicals using xanthine and xanthine oxidase in vitro. As a result, middle molecular weight heparinyl phenylalanine, middle molecular weight heparinyl leucine, and middle molecular weight heparinyl tyrosine showed significant protective effects on HUV-ECs. In conclusion, these three HE derivatives might be candidates for therapeutic agents to treat diseases attributed to peroxidation.
Amino Acid Composition, Molecular Weight Distribution and Antioxidant Stability of Shrimp Processing Byproduct Hydrolysate  [PDF]
J. Zhao,G.R. Huang,M.N. Zhang,W.W. Chen
American Journal of Food Technology , 2011,
Abstract: Protein hydrolysate have many practical applications in a various of industries due to the bioactive peptides related to their amino acid composition, sequence and molecular weight. The amino acid composition, molecular weight distribution and antioxidant stability of alcalase hydrolysate were investigated in this study. The hydrolysate was separated into five fractions by ultra filtration system with different molecular weight cutoff with 10, 5, 3 and 1 kDa, respectively. The protein content, 1,1-diphenyl-2-picrylhydrazyl radical scavenging activity and molecular weight of each fraction were determined. In addition, the antioxidant stability of the hydrolysate under several operating conditions was studied. The results showed that the hydrolysate was composed with high amounts of hydrophobic amino acids (40.4%) which might contribute to the high antioxidant activity. The fraction with molecular weight lower than 1 kDa exhibited the highest antioxidative activity among the five fractions. The antioxidant stability experiments showed that the hydrolysate was stable when it was heated up to 100C and the relative antioxidative activity could be maintained nearly 70% at very low pH of 2.0. Glucose and sucrose had negative effects on the antioxidative activity, in which the relative activity of about 80% was retained. Sodium chloride and sodium benzoate had little or no effects on the antioxidative activity of the hydrolysate. The effects of Zn2+ and Cu2+ on the antioxidative activity were significant and dependent on metal concentration. The shrimp processing byproduct hydrolysate may be a potential natural food antioxidant in the future.
Single amino acid substitution in important hemoglobinopathies does not disturb molecular function and biological process  [cached]
Viroj Wiwanitkit
International Journal of Nanomedicine , 2008,
Abstract: Viroj WiwanitkitDepartment of Laboratory Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, ThailandAbstract: Hemoglobin is an important protein found in the red cells of many animals. In humans, the hemoglobin is mainly distributed in the red blood cell. Single amino acid substitution is the main pathogenesis of most hemoglobin disorders. Here, the author used a new gene ontology technology to predict the molecular function and biological process of four important hemoglobin disorders with single substitution. The four studied important abnormal hemoglobins (Hb) with single substitution included Hb S, Hb E, Hb C, and Hb J-Baltimore. Using the GoFigure server, the molecular function and biological process in normal and abnormal hemoglobins was predicted. Compared with normal hemoglobin, all studied abnormal hemoglobins had the same function and biological process. This indicated that the overall function of oxygen transportation is not disturbed in the studied hemoglobin disorders. Clinical findings of oxygen depletion in abnormal hemoglobin should therefore be due to the other processes rather than genomics, proteomics, and expression levels.Keywords: hemoglobin, amino acid, substitution, function
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