Day after day, the importance of relying on nature in many fields such as food, medical, pharmaceutical industries, and others is increasing. Essential oils (EOs) are considered as one of the most significant natural products for use as antimicrobials, antioxidants, antitumorals, and anti-inflammatories. Optimizing the usage of EOs is a big challenge faced by the scientific researchers because of the complexity of chemical composition of every EO, in addition to the difficulties to determine the best in inhibiting the bacterial activity. Read More
Next-generation sequencing technology has provided resources to easily explore and identify candidate single-nucleotide polymorphisms (SNPs) and variants. However, there remains a challenge in identifying and inferring the causal SNPs from sequence data. A problem with different methods that predict the effect of mutations is that they produce false positives. Read More
Currently, time-consuming serial in vitro experimentation involving immunocytochemistry or radiolabeled materials is required to identify which of the numerous Rab-GTPases (Rab) and Rab-GTPase activating proteins (RabGAP) are capable of functional interactions. These interactions are essential for numerous cellular functions, and in silico methods of reducing in vitro trial and error would accelerate the pace of research in cell biology. We have utilized a combination of three-dimensional protein modeling and protein bioinformatics to identify domains present in Rab proteins that are predictive of their functional interaction with a specific RabGAP. Read More
Sequencing the actinomycin (acm) biosynthetic gene cluster of Streptomyces antibioticus IMRU 3720, which produces actinomycin X (Acm X), revealed 20 genes organized into a highly similar framework as in the bi-armed acm C biosynthetic gene cluster of Streptomyces chrysomallus but without an attached additional extra arm of orthologues as in the latter. Curiously, the extra arm of the S. chrysomallus gene cluster turned out to perfectly match the single arm of the S. Read More
Ebola virus (EBOV) is one of the lethal viruses, causing more than 24 epidemic outbreaks to date. Despite having available molecular knowledge of this virus, no definite vaccine or other remedial agents have been developed yet for the management and avoidance of EBOV infections in humans. Disclosing this, the present study described an epitope-based peptide vaccine against EBOV, using a combination of B-cell and T-cell epitope predictions, followed by molecular docking and molecular dynamics simulation approach. Read More
Purpose: Evidence suggests that circulating serum microRNAs (miRNAs) might preferentially target immune-related mRNAs. If this were the case, we hypothesized that immune-related mRNAs would have more predicted serum miRNA binding sites than other mRNAs and, reciprocally, that serum miRNAs would have more immune-related mRNA targets than non-serum miRNAs.
Materials And Methods: We developed a consensus target predictor using the random forest framework and calculated the number of predicted miRNA-mRNA interactions in various subsets of miRNAs (serum, non-serum) and mRNAs (immune related, nonimmune related). Read More
New molecular modeling approaches, driven by rapidly improving computational platforms, have allowed many success stories for the use of computer-assisted drug design in the discovery of new mechanism-or structure-based drugs. In this overview, we highlight three aspects of the use of molecular docking. First, we discuss the combination of molecular and quantum mechanics to investigate an unusual enzymatic mechanism of a flavoprotein. Read More
Adv Appl Bioinform Chem 2015 8;8:49-63. Epub 2015 Dec 8.
Biochemistry and Molecular Biology Department, Jahangirnagar University, Savar, Bangladesh ; Division of Parasitology, Department of Infectious Diseases, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan.
Bacterial enteric infections resulting in diarrhea, dysentery, or enteric fever constitute a huge public health problem, with more than a billion episodes of disease annually in developing and developed countries. In this study, the deadly agent of hemorrhagic diarrhea and hemolytic uremic syndrome, Escherichia coli O157:H7 was investigated with extensive computational approaches aimed at identifying novel and broad-spectrum antibiotic targets. A systematic in silico workflow consisting of comparative genomics, metabolic pathways analysis, and additional drug prioritizing parameters was used to identify novel drug targets that were essential for the pathogen's survival but absent in its human host. Read More
Today's genomic experiments have to process the so-called "biological big data" that is now reaching the size of Terabytes and Petabytes. To process this huge amount of data, scientists may require weeks or months if they use their own workstations. Parallelism techniques and high-performance computing (HPC) environments can be applied for reducing the total processing time and to ease the management, treatment, and analyses of this data. Read More
Adv Appl Bioinform Chem 2015 19;8:37-47. Epub 2015 Nov 19.
Joint BSC-IRB Research Program in Computational Biology, University of Barcelona, Barcelona, Spain ; Barcelona Supercomputing Center, University of Barcelona, Barcelona, Spain ; Department of Biochemistry and Molecular Biology, University of Barcelona, Barcelona, Spain.
Molecular dynamics simulations have evolved into a mature technique that can be used effectively to understand macromolecular structure-to-function relationships. Present simulation times are close to biologically relevant ones. Information gathered about the dynamic properties of macromolecules is rich enough to shift the usual paradigm of structural bioinformatics from studying single structures to analyze conformational ensembles. Read More
Biological pathways have become the standard way to represent the coordinated reactions and actions of a series of molecules in a cell. A series of interconnected pathways is referred to as a biological network, which denotes a more holistic view on the entanglement of cellular reactions. Biological pathways and networks are not only an appropriate approach to visualize molecular reactions. Read More
Crimean-Congo hemorrhagic fever (CCHF) is a tick-borne zoonotic viral disease with a disease fatality rate between 15% and 70%. Despite the wide range of distribution, the virus (CCHFV) is basically endemic in Africa, Asia, eastern Europe, and the Middle East. Acute febrile illness associated with petechiae, disseminated intravascular coagulation, and multiple-organ failure are the main symptoms of the disease. Read More
Purpose: Streptococcus sanguinis is a Gram-positive, facultative aerobic bacterium that is a member of the viridans streptococcus group. It is found in human mouths in dental plaque, which accounts for both dental cavities and bacterial endocarditis, and which entails a mortality rate of 25%. Although a range of remedial mediators have been found to control this organism, the effectiveness of agents such as penicillin, amoxicillin, trimethoprim-sulfamethoxazole, and erythromycin, was observed. Read More
The last influenza A pandemic provided an excellent opportunity to study the adaptation of the influenza A(H1N1)pdm09 virus to the human host. Particularly, due to the availability of sequences taken from isolates since the beginning of the pandemic until date, we could monitor amino acid changes that occurred in the hemagglutinin (HA) as the virus spread worldwide and became the dominant H1N1 strain. HA is crucial to viral infection because it binds to sialidated cell-receptors and mediates fusion of cell and viral membranes; because antibodies that bind to HA may block virus entry to the cell, this protein is subjected to high selective pressure. Read More
The blood-brain barrier choline transporter (BBB-ChT) may have utility as a drug delivery vector to the central nervous system (CNS). We therefore initiated molecular docking studies with the AutoDock and AutoDock Vina (ADVina) algorithms to develop predictive models for compound screening and to identify structural features important for binding to this transporter. The binding energy predictions were highly correlated with r(2) =0. Read More
The cytochrome P450 (CYP)3A4 enzyme affects the metabolism of most drug-like substances, and its inhibition may influence drug safety. Modulation of CYP3A4 by flavonoids, such as anthocyanins, has been shown to inhibit the mutagenic activity of mammalian cells. Considering the previous investigations addressing CYP3A4 inhibition by these substances, we studied the three-dimensional quantitative structure-activity relationship (3D-QSAR) in a series of anthocyanin derivatives as CYP3A4 inhibitors. Read More
P-glycoprotein (P-gp) is an ATP (adenosine triphosphate)-binding cassette transporter that causes multidrug resistance of various chemotherapeutic substances by active efflux from mammalian cells. P-gp plays a pivotal role in limiting drug absorption and distribution in different organs, including the intestines and brain. Thus, the prediction of P-gp-drug interactions is of vital importance in assessing drug pharmacokinetic and pharmacodynamic properties. Read More
Probing protein-deoxyribonucleic acid (DNA) is gaining popularity as it sheds light on molecular mechanisms that regulate the expression of genes. Currently, tiling-arrays and next-generation sequencing technology can be used to measure these interactions. Both methods generate a signal over the genome in which contiguous regions of peaks on the genome represent the presence of an interacting molecule. Read More
Viral neuraminidase inhibitors such as oseltamivir and zanamivir prevent early virus multiplication by blocking sialic acid cleavage on host cells. These drugs are effective for the treatment of a variety of influenza subtypes, including swine flu (H1N1). The binding site for these drugs is well established and they were designed based on computational docking studies. Read More
Foot and mouth disease virus (FMDV), with its seven serotypes, is a highly contagious virus infecting mainly cloven-hoofed animals. The serotype Asia1 occurs mainly in Asian regions. An in-silico approach was taken to reveal the antigenic heterogeneities within the capsid protein VP1 of Asia1. Read More
Conventional methods to analyze genome-wide association studies and whole exome or whole genome sequencing studies would be prone to overlook variants which might exert a recessive effect on risk of disease, either as homozygotes or compound heterozygotes. It is plausible that such effects may be common even in outbred populations. An approach is described which is based on identifying a set of variants in a gene as being potentially of interest and then testing whether there is an excess of cases who are either homozygotes or complex heterozygotes for these variants. Read More
Adv Appl Bioinform Chem 2013 10;6:15-27. Epub 2013 May 10.
Center for Bioinformatics and Computational Biology, Department of Biology, Jackson State University, Jackson, MS, USA ; Department of Environmental Sciences, College of Agriculture and Environmental Sciences, University of South Africa, Pretoria, South Africa.
Background: Human schistosomiasis is a freshwater snail-transmitted disease caused by parasitic flatworms of the Schistosoma genus. Schistosoma haematobium, Schistosoma mansoni, and Schistosoma japonicum are the three major species infecting humans. These parasites undergo a complex developmental life cycle, in which they encounter a plethora of environmental signals. Read More
The equity of a drug target is principally evaluated by its genetic vulnerability with tools ranging from antisense- and microRNA-driven knockdowns to induced expression of the target protein. In order to upgrade the process of antibacterial target identification and discern its most effective type of inhibition, an in silico toolbox that evaluates its genetic and chemical vulnerability leading either to stasis or cidal outcome was constructed and validated. By precise simulation and careful experimentation using enolpyruvyl shikimate-3-phosphate synthase and its specific inhibitor glyphosate, it was shown that genetic knockdown is distinct from chemical knockdown. Read More
Evaluation of docking results is one of the most important problems for virtual screening and in silico drug design. Modern approaches for the identification of active compounds in a large data set of docked molecules use energy scoring functions. One of the general and most significant limitations of these methods relates to inaccurate binding energy estimation, which results in false scoring of docked compounds. Read More
Department of Biological Sciences, Graduate School of Biosciences and Biotechnology, Tokyo Institute of Technology, Tokyo, Japan ; Graduate School of Information Sciences, Tohoku University, Miyagi, Japan.
Objective: With the dramatic increase in microarray data, biclustering has become a promising tool for gene expression analysis. Biclustering has been proven to be superior over clustering in identifying multifunctional genes and searching for co-expressed genes under a few specific conditions; that is, a subgroup of all conditions. Biclustering based on a genetic algorithm (GA) has shown better performance than greedy algorithms, but the overlap state for biclusters must be treated more systematically. Read More
The ability to predict immunogenic regions in selected proteins by in-silico methods has broad implications, such as allowing a quick selection of potential reagents to be used as diagnostics, vaccines, immunotherapeutics, or research tools in several branches of biological and biotechnological research. However, the prediction of antibody target sites in proteins using computational methodologies has proven to be a highly challenging task, which is likely due to the somewhat elusive nature of B-cell epitopes. This paper proposes a web-based platform for scoring potential immunological reagents based on the structures or 3D models of the proteins of interest. Read More
Previously described methods for the combined analysis of common and rare variants have disadvantages such as requiring an arbitrary classification of variants or permutation testing to assess statistical significance. Here we propose a novel method which implements a weighting scheme based on allele frequencies observed in both cases and controls. Because the test is unbiased, scores can be analyzed with a standard t-test. Read More
Shwachman-Bodian-Diamond syndrome (SBDS) is linked to a mutation in a single gene. The SBDS proinvolved in RNA metabolism and ribosome-associated functions, but SBDS mutation is primarily linked to a defect in polymorphonuclear leukocytes unable to orient correctly in a spatial gradient of chemoattractants. Results of data mining and comparative genomic approaches undertaken in this study suggest that SBDS protein is also linked to tRNA metabolism and translation initiation. Read More
Gene set enrichment analysis for analyzing large profiling and screening experiments can reveal unifying biological schemes based on previously accumulated knowledge represented as "gene sets". Most of the existing implementations use a fixed fold-change or P value cutoff to generate regulated gene lists. However, the threshold selection in most cases is arbitrary, and has a significant effect on the test outcome and interpretation of the experiment. Read More
Background: The human progesterone receptor (hPR) belongs to the steroid receptor family. It may be found as monomers (A and B) and or as a dimer (AB). hPR is regarded as the prognostic biomarker for breast cancer. Read More
Purpose: Here we describe LifePrint, a sequence alignment-independent k-tuple distance method to estimate relatedness between complete genomes.
Methods: We designed a representative sample of all possible DNA tuples of length 9 (9-tuples). The final sample comprises 1878 tuples (called the LifePrint set of 9-tuples; LPS9) that are distinct from each other by at least two internal and noncontiguous nucleotide differences. Read More
Artificially synthesized RNA molecules have recently come under study since such molecules have a potential for creating a variety of novel functional molecules. When designing artificial RNA sequences, secondary structure should be taken into account since functions of noncoding RNAs strongly depend on their structure. RNA inverse folding is a methodology for computationally exploring the RNA sequences folding into a user-given target structure. Read More
Follistatin has been reported as a candidate gene for polycystic ovarian syndrome (PCOS) based on linkage and association studies. In this study, investigation of polymorphisms in the FST gene was done to determine if genetic variation is associated with susceptibility to PCOS. The nucleotide sequence of human follistatin and the protein sequence of human follistatin were retrieved from the NCBI database using Entrez. Read More
Background: A prerequisite for a successful design and discovery of an antibacterial drug is the identification of essential targets as well as potent inhibitors that adversely affect the survival of bacteria. In order to understand how intracellular perturbations occur due to inhibition of essential metabolic pathways, we have built, through the use of ordinary differential equations, a mathematical model of 8 major Escherichia coli pathways.
Results: Individual in vitro enzyme kinetic parameters published in the literature were used to build the network of pathways in such a way that the flux distribution matched that reported from whole cells. Read More
Purpose: Interest in developing methods appropriate for mapping increasing amounts of genome-wide molecular data are increasing rapidly. There is also an increasing need for methods that are able to efficiently simulate such data.
Patients And Methods: In this article, we provide a graph-theory approach to find the necessary and sufficient conditions for the existence of a phylogeny matrix with k nonidentical haplotypes, n single nucleotide polymorphisms (SNPs), and a population size of m for which the minimum allele frequency of each SNP is between two specific numbers a and b. Read More
We present a two-phase strategy for optimizing a multidimensional, nonconvex function arising during genetic mapping of quantitative traits. Such traits are believed to be affected by multiple so called quantitative trait loci (QTL), and searching for d QTL results in a d-dimensional optimization problem with a large number of local optima. We combine the global algorithm DIRECT with a number of local optimization methods that accelerate the final convergence, and adapt the algorithms to problem-specific features. Read More
Many segmentation techniques have been published, and some of them have been widely used in different application problems. Most of these segmentation techniques have been motivated by specific application purposes. Unsupervised methods, which do not assume any prior scene knowledge can be learned to help the segmentation process, and are obviously more challenging than the supervised ones. Read More
In recent years, due to vital need for novel fungicidal agents, investigation on natural antifungal resources has been increased. The special features exhibited by neural network classifiers make them suitable for handling complex problems like analyzing different properties of candidate compounds in computer-aided drug design. In this study, by using a Levenberg-Marquardt (LM) neural network (the fastest of the training algorithms), the relation between some important thermodynamic and physico-chemical properties of coumarin compounds and their biological activities (tested against Candida albicans) has been evaluated. Read More
This paper discusses cyberinformation studies of the amino acid composition of insulin, in particular the identification of scientific terminology that could describe this phenomenon, ie, the study of genetic information, as well as the relationship between the genetic language of proteins and theoretical aspects of this system and cybernetics. The results of this research show that there is a matrix code for insulin. It also shows that the coding system within the amino acid language gives detailed information, not only on the amino acid "record", but also on its structure, configuration, and various shapes. Read More
Chronic hepatitis C (CHC) patients often stop pursuing interferon-alfa and ribavirin (IFN-alfa/RBV) treatment because of the high cost and associated adverse effects. It is highly desirable, both clinically and economically, to establish tools to distinguish responders from nonresponders and to predict possible outcomes of the IFN-alfa/RBV treatments. Single nucleotide polymorphisms (SNPs) can be used to understand the relationship between genetic inheritance and IFN-alfa/RBV therapeutic response. Read More
We explore, using the Crh protein dimer as a model, how information from solution NMR, solid-state NMR and X-ray crystallography can be combined using structural bioinformatics methods, in order to get insights into the transition from solution to crystal. Using solid-state NMR chemical shifts, we filtered intra-monomer NMR distance restraints in order to keep only the restraints valid in the solid state. These filtered restraints were added to solid-state NMR restraints recorded on the dimer state to sample the conformational landscape explored during the oligomerization process. Read More
In this study we used a Random Forest-based approach for an assignment of small guanosine triphosphate proteins (GTPases) to specific subgroups. Small GTPases represent an important functional group of proteins that serve as molecular switches in a wide range of fundamental cellular processes, including intracellular transport, movement and signaling events. These proteins have further gained a special emphasis in cancer research, because within the last decades a huge variety of small GTPases from different subgroups could be related to the development of all types of tumors. Read More
Objective: To construct and optimize a neural network that is capable of predicting the occurrence of recurrent aphthous ulceration (RAU) based on a set of appropriate input data.
Participants And Methods: Artificial neural networks (ANN) software employing genetic algorithms to optimize the architecture neural networks was used. Input and output data of 86 participants (predisposing factors and status of the participants with regards to recurrent aphthous ulceration) were used to construct and train the neural networks. Read More
Ca(2+)-ions have a range of affinities to different proteins, depending on the various functions of these proteins. This makes the determination of Ca(2+)-protein affinities an interesting subject for functional studies. We have investigated the performance of two methods - Fold-X and AutoDock vina - in the prediction of Ca(2+)-protein affinities. Read More
Genotoxic stress is induced by a broad range of DNA-damaging agents and could lead to a variety of human diseases including cancer. DNA damage is also therapeutically induced for cancer treatment with the aim to eliminate tumor cells. However, the effectiveness of radio- and chemotherapy is strongly hampered by tumor cell resistance. Read More
In recent years, protein-protein interactions are becoming the object of increasing attention in many different fields, such as structural biology, molecular biology, systems biology, and drug discovery. From a structural biology perspective, it would be desirable to integrate current efforts into the structural proteomics programs. Given that experimental determination of many protein-protein complex structures is highly challenging, and in the context of current high-performance computational capabilities, different computer tools are being developed to help in this task. Read More
Protein-protein docking simulations can provide the predicted complex structural models. In a docking simulation, several putative structural models are selected by scoring functions from an ensemble of many complex models. Scoring functions based on statistical analyses of heterodimers are usually designed to select the complex model with the most abundant interaction mode found among the known complexes, as the correct model. Read More
The large numbers of protein sequences generated by whole genome sequencing projects require rapid and accurate methods of annotation. The detection of homology through computational sequence analysis is a powerful tool in determining the complex evolutionary and functional relationships that exist between proteins. Homology search algorithms employ amino acid substitution matrices to detect similarity between proteins sequences. Read More
Multivariate partial least square (PLS) regression allows the modeling of complex biological events, by considering different factors at the same time. It is unaffected by data collinearity, representing a valuable method for modeling high-dimensional biological data (as derived from genomics, proteomics and peptidomics). In presence of multiple responses, it is of particular interest how to appropriately "dissect" the model, to reveal the importance of single attributes with regard to individual responses (for example, variable selection). Read More
Identification of genes involved in the aging process is critical for understanding the mechanisms of age-dependent diseases such as cancer and diabetes. Measuring the mutant gene lifespan, each missing one gene, is traditionally employed to identify longevity genes. While such screening is impractical for the whole genome due to the time-consuming nature of lifespan assays, it can be achieved by in silico genetic manipulations with systems biology approaches. Read More