Improving Structural Features Prediction in Protein Structure Modeling

Proteins play a vital role in the biological activities of all living species. In nature, a protein folds into a specific and energetically favorable three-dimensional structure which is critical to its biological function. Hence, there has been a great effort by researchers in both experimentally determining and computationally predicting the structures of proteins. The current experimental methods of protein structure determination are complicated, time-consuming, and expensive. On the other hand, the sequencing of proteins is fast, simple, and relatively less expensive. Thus, the gap between the number of known sequences and the determined structures is growing, and is expected to keep expanding. In contrast, computational approaches that can generate three-dimensional protein models with high resolution are attractive, due to their broad economic and scientific impacts. Accurately predicting protein structural features, such as secondary structures, disulfide bonds, and solvent accessibility is a critical intermediate step stone to obtain correct three-dimensional models ultimately. In this dissertation, we report a set of approaches for improving the accuracy of structural features prediction in protein structure modeling. First of all, we derive a statistical model to generate context-based scores characterizing the favorability of segments of residues in adopting certain structural features. Then, together with other information such as evolutionary and sequence information, we incorporate the context-based scores in machine learning approaches to predict secondary structures, disulfide bonds, and solvent accessibility. Furthermore, we take advantage of the emerging high performance computing architectures in GPU to accelerate the calculation of pairwise and high-order interactions in context-based scores. Finally, we make these prediction methods available to the public via web services and software packages

Dinosolve: A Protein Disulfide Bonding Prediction Server Using Context-Based Features to Enhance Prediction Accuracy

Background: Disulfide bonds play an important role in protein folding and structure stability. Accurately predicting disulfide bonds from protein sequences is important for modeling the structural and functional characteristics of many proteins. Methods: In this work, we introduce an approach of enhancing disulfide bonding prediction accuracy by taking advantage of context-based features. We firstly derive the first-order and second-order mean-force potentials according to the amino acid environment around the cysteine residues from large number of cysteine samples. The mean-force potentials are integrated as context-based scores to estimate the favorability of a cysteine residue in disulfide bonding state as well as a cysteine pair in disulfide bond connectivity. These context-based scores are then incorporated as features together with other sequence and evolutionary information to train neural networks for disulfide bonding state prediction and connectivity prediction. Results: The 10-fold cross validated accuracy is 90.8% at residue-level and 85.6% at protein-level in classifying an individual cysteine residue as bonded or free, which is around 2% accuracy improvement. The average accuracy for disulfide bonding connectivity prediction is also improved, which yields overall sensitivity of 73.42% and specificity of 91.61%. Conclusions: Our computational results have shown that the context-based scores are effective features to enhance the prediction accuracies of both disulfide bonding state prediction and connectivity prediction. Our disulfide prediction algorithm is implemented on a web server named Dinosolve available at: http://hpcr.cs.odu.edu/dinosolve

Template-Based C8-Scorpion: A Protein 8 State Secondary Structure Prediction Method Using Structural Information and Context-Based Features

Background: Secondary structures prediction of proteins is important to many protein structure modeling applications. Correct prediction of secondary structures can significantly reduce the degrees of freedom in protein tertiary structure modeling and therefore reduces the difficulty of obtaining high resolution 3D models. Methods: In this work, we investigate a template-based approach to enhance 8-state secondary structure prediction accuracy. We construct structural templates from known protein structures with certain sequence similarity. The structural templates are then incorporated as features with sequence and evolutionary information to train two-stage neural networks. In case of structural templates absence, heuristic structural information is incorporated instead. Results: After applying the template-based 8-state secondary structure prediction method, the 7-fold cross-validated Q8 accuracy is 78.85%. Even templates from structures with only 20% ~ 30% sequence similarity can help improve the 8-state prediction accuracy. More importantly, when good templates are available, the prediction accuracy of less frequent secondary structures, such as 3-10 helices, turns, and bends, are highly improved, which are useful for practical applications. Conclusions: Our computational results show that the templates containing structural information are effective features to enhance 8-state secondary structure predictions. Our prediction algorithm is implemented on a web server named C8-SCORPION available at: http://hpcr.cs.odu.edu/c8scorpion

FLEXc: Protein Flexibility Prediction Using Context-Based Statistics, Predicted Structural Features, and Sequence Information

The fluctuation of atoms around their average positions in protein structures provides important information regarding protein dynamics. This flexibility of protein structures is associated with various biological processes. Predicting flexibility of residues from protein sequences is significant for analyzing the dynamic properties of proteins which will be helpful in predicting their functions

Performance of Recombinant rK39 antigen in the diagnosis of Leishmaniasis

Background: Recombinant K39 antigen test is one of the recent experiences in rapid diagnosis of Visceral Leishmaniasis ,it consist  of 39 amino acid which represent the main component of the protein of the Leishmania  parasite and that the reaction occurs between the antibodies in the serum and antigens blotted in the rK39 strip test.                                                                                       Objective: Find out possible reaction of rK39 antigen test on other diseases than visceral leishmaniasis, as well as to compare the test results on both serum and urine of same patients. Patients and Methods: A total of 65 blood and urine samples were included in the study; 25 patients with cutaneous leishmaniasis attended Baquba Teaching Hospital, and 40 apparently healthy controls.  All serum and urine samples were tested with rK39 strip test. 15 serum samples were randomly selected and Indirect Fluorescent Antibody Techniques for diagnosis of Leishmaniasis for the purpose of comparison of rK39 strip test. Results: There was highly significant differences when using the rK39 strip test in urine and serum in patients infected with cutaneous leishmaniasis  (P <0.05), and no significant difference between the sexes, as well as age group , as well as the absence of a significant difference between the rK39 strip test and Indirect Fluorescent Antibody Techniques. Conclusion: rK39 strip antigen test gives positive results, may be due to greater phylogenetic proximity between Leishmania species, or due to mixed infection with Visceral Leishmaniasis

Factors Influencing Use of Information and Communication Technologies among Farmers in Rural Punjab, Pakistan

This study explored the factors influencing the application of Information and Communication Technologies (ICTs) among farmers in the Punjab province of Pakistan. The Punjab province is divided into three agro-ecological zones viz Northern, Central and Southern. In this study, one district from each zone was randomly selected. Total sample size comprises of 150 farmers. Farmers were interviewed using a self-administered interview schedule comprising of open and close-ended questions. Respondents’ access to ICTs was low level. Chi-square test revealed a significant association between the age of respondents and adoption of ICTs. Young respondents were leading users of ICTs in the study area. Size of landholding and income level of the respondents had a significant association with the frequency of use of ICTs in agriculture. Among various ICTs tools, mobile/cell phone attracted 47.3% of respondents to access agricultural information. Factors militating use of ICTs include; electricity/power issues (x̄=2.95/3.00), language barriers (x̄=2.93/3.00), limited knowledge and skills about ICTs (x̄=2.89/3.00), high cost (x̄=2.87/3.00) and limited availability of ICTs (x̄=2.85/3.00). Extent of ICTs use to access agricultural information can surge with the unit income level rise, enhanced access to ICTs and enhanced skill level to use ICTs

Factors Influencing Use of Information and Communication Technologies among Farmers in Rural Punjab, Pakistan

This study explored the factors influencing the application of Information and Communication Technologies (ICTs) among farmers in the Punjab province of Pakistan. The Punjab province is divided into three agro-ecological zones viz Northern, Central and Southern. In this study, one district from each zone was randomly selected. Total sample size comprises of 150 farmers. Farmers were interviewed using a self-administered interview schedule comprising of open and close-ended questions. Respondents’ access to ICTs was low level. Chi-square test revealed a significant association between the age of respondents and adoption of ICTs. Young respondents were leading users of ICTs in the study area. Size of landholding and income level of the respondents had a significant association with the frequency of use of ICTs in agriculture. Among various ICTs tools, mobile/cell phone attracted 47.3% of respondents to access agricultural information. Factors militating use of ICTs include; electricity/power issues (x̄=2.95/3.00), language barriers (x̄=2.93/3.00), limited knowledge and skills about ICTs (x̄=2.89/3.00), high cost (x̄=2.87/3.00) and limited availability of ICTs (x̄=2.85/3.00). Extent of ICTs use to access agricultural information can surge with the unit income level rise, enhanced access to ICTs and enhanced skill level to use ICTs

Synthesis and Identification of New N,N-Disubstituted Thiourea, and Thiazolidinone Scaffolds Based on Quinolone Moiety as Urease Inhibitor

Synthesis of thiazolidinone based on quinolone moiety was established starting from 4-hydroxyquinol-2-ones. The strategy started with the reaction of ethyl bromoacetate with 4-hydroxyquinoline to give the corresponding ethyl oxoquinolinyl acetates, which reacted with hydrazine hydrate to afford the hydrazide derivatives. Subsequently, hydrazides reacted with isothiocyanate derivatives to give the corresponding N,N-disubstituted thioureas. Finally, on subjecting the N,N-disubstituted thioureas with dialkyl acetylenedicarboxylates, cyclization occurred, and thiazolidinone derivatives were obtained in good yields. The two series based on quinolone moiety, one containing N,N-disubstituted thioureas and the other containing thiazolidinone functionalities, were screened for their in vitro urease inhibition properties using thiourea and acetohydroxamic acid as standard inhibitors. The inhibition values of the synthesized thioureas and thiazolidinones exhibited moderate to good inhibitory effects. The structure−activity relationship revealed that N-methyl quinolonyl moiety exhibited a superior effect, since it was proved to be the most potent inhibitor in the present series achieving (IC50 = 1.83 ± 0.79 µM). The previous compound exhibited relatively much greater activity, being approximately 12-fold more potent than thiourea and acetohydroxamic acid as references. Molecular docking analysis showed a good protein−ligand interaction profile against the urease target (PDBID: 4UBP), emphasizing the electronic and geometric effect of N,N-disubstituted thiourea. View Full-Tex

Regioselective formation of new 3-S-alkylated-1,2,4-triazole-quinolones

Regioselective synthesis of quinolone-1,2,4-triazoles was established starting from 4-hydroxyquinol-2-ones. The strategy started by the reaction of ethyl bromoacetate with 4-hydroxyquinoline to give the corresponding ethyl oxoquinolinyl acetates, which reacted with hydrazine hydrate to afford the hydrazide derivatives. Subsequently, hydrazides reacted with isothiocyanate derivatives to give the corresponding acyl thiosemicarbazides. Finally, subjecting the thiosemicarbazide derivatives with ethyl bromoacetate, the reaction underwent internal cyclization and alkylation processes. Alkylation occurred regioselectivity to the sulfur atom of the thione group and not to the amino group. Thus 3-S-1,2,4-triazole-quinolones were obtained in good yields. The structure of the obtained compounds was proved by different spectroscopic techniques together with elemental analysis and X-ray crystallography.Peer reviewe