Mehdi Sadeghi | Iran University of Medical Sciences (original) (raw)

Papers by Mehdi Sadeghi

PLoS ONE, 2014

Decision making at a cellular level determines different fates for isogenic cells. However, it is... more Decision making at a cellular level determines different fates for isogenic cells. However, it is not yet clear how rational decisions are encoded in the genome, how they are transmitted to their offspring, and whether they evolve and become optimized throughout generations. In this paper, we use a game theoretic approach to explain how rational decisions are made in the presence of cooperators and competitors. Our results suggest the existence of an internal switch that operates as a biased coin. The biased coin is, in fact, a biochemical bistable network of interacting genes that can flip to one of its stable states in response to different environmental stimuli. We present a framework to describe how the positions of attractors in such a gene regulatory network correspond to the behavior of a rational player in a competing environment. We evaluate our model by considering lysis/lysogeny decision making of bacteriophage lambda in E. coli.

Biosystems, 2014

One of the fundamental problems in bioinformatics is phylogenetic tree reconstruction, which can ... more One of the fundamental problems in bioinformatics is phylogenetic tree reconstruction, which can be used for classifying living organisms into different taxonomic clades. The classical approach to this problem is based on a marker such as 16S ribosomal RNA. Since evolutionary events like genomic rearrangements are not included in reconstructions of phylogenetic trees based on single genes, much effort has been made to find other characteristics for phylogenetic reconstruction in recent years. With the increasing availability of completely sequenced genomes, gene order can be considered as a new solution for this problem. In the present work, we applied maximal common intervals (MCIs) in two or more genomes to infer their distance and to reconstruct their evolutionary relationship. Additionally, measures based on uncommon segments (UCS's), i.e., those genomic segments which are not detected as part of any of the MCIs, are also used for phylogenetic tree reconstruction. We applied these two types of measures for reconstructing the phylogenetic tree of 63 prokaryotes with known COG (clusters of orthologous groups) families. Similarity between the MCI-based (resp. UCS-based) reconstructed phylogenetic trees and the phylogenetic tree obtained from NCBI taxonomy browser is as high as 93.1% (resp. 94.9%). We show that in the case of this diverse dataset of prokaryotes, tree reconstruction based on MCI and UCS outperforms most of the currently available methods based on gene orders, including breakpoint distance and DCJ. We additionally tested our new measures on a dataset of 13 closely-related bacteria from the genus Prochlorococcus. In this case, distances like rearrangement distance, breakpoint distance and DCJ proved to be useful, while our new measures are still appropriate for phylogenetic reconstruction.

Proteins-structure Function and Bioinformatics, 2009

tially summation of pairwise electrostatic and Van der Waals interaction energies, bonds, angles ... more tially summation of pairwise electrostatic and Van der Waals interaction energies, bonds, angles and dihedral angles terms. 11-14 In addition, terms such as entropy and solvent effect are implicitly included. Although physical energy function is widely used in molecular dynamic simulation of proteins, these functions have been out of favor in protein structure prediction because of their greater computational costs. To reduce computational complexity of the protein folding problem, knowledge-based or empirical mean force potential is widely used. The structure of folded proteins reflects the energy of the interaction of all their components, including all enthalpic and entropic contributions, as well as solvent effects.

Journal of Bioinformatics and Computational Biology

Protein-protein interactions (PPIs) are important for understanding the cellular mechanisms of bi... more Protein-protein interactions (PPIs) are important for understanding the cellular mechanisms of biological functions, but the reliability of PPIs extracted by high-throughput assays is known to be low. To address this, many current methods use multiple evidence from different sources of information to compute reliability scores for such PPIs. However, they often combine the evidence without taking into account the uncertainty of the evidence values, potential dependencies between the information sources used and missing values from some information sources. We propose to formulate the task of scoring PPIs using multiple information sources as a multi-criteria decision making problem that can be solved using data fusion to model potential interactions between the multiple information sources. Using data fusion, the amount of contribution from each information source can be proportioned accordingly to systematically score the reliability of PPIs. Our experimental results showed that th...

ChemInform

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was e... more ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

BMC Bioinformatics

Motivation: Although there are many different algorithms and software tools for aligning sequenci... more Motivation: Although there are many different algorithms and software tools for aligning sequencing reads, fast gapped sequence search is far from solved. Strong interest in fast alignment is best reflected in the $10 6 prize for the Innocentive competition on aligning a collection of reads to a given database of reference genomes. In addition, de novo assembly of next-generation sequencing long reads requires fast overlap-layout-concensus algorithms which depend on fast and accurate alignment. Contribution: We introduce ARYANA, a fast gapped read aligner, developed on the base of BWA indexing infrastructure with a completely new alignment engine that makes it significantly faster than three other aligners: Bowtie2, BWA and SeqAlto, with comparable generality and accuracy. Instead of the time-consuming backtracking procedures for handling mismatches, ARYANA comes with the seed-and-extend algorithmic framework and a significantly improved efficiency by integrating novel algorithmic t...

BMC Systems Biology, 2015

Background: Understanding the mechanisms by which hundreds of diverse cell types develop from a s... more Background: Understanding the mechanisms by which hundreds of diverse cell types develop from a single mammalian zygote has been a central challenge of developmental biology. Conrad H. Waddington, in his metaphoric "epigenetic landscape" visualized the early embryogenesis as a hierarchy of lineage bifurcations. In each bifurcation, a single progenitor cell type produces two different cell lineages. The tristable dynamical systems are used to model the lineage bifurcations. It is also shown that a genetic circuit consisting of two auto-activating transcription factors (TFs) with cross inhibitions can form a tristable dynamical system. Results: We used gene expression profiles of pre-implantation mouse embryos at the single cell resolution to visualize the Waddington landscape of the early embryogenesis. For each lineage bifurcation we identified two clusters of TFsrather than two single TFs as previously proposedthat had opposite expression patterns between the pair of bifurcated cell types. The regulatory circuitry among each pair of TF clusters resembled a genetic circuit of a pair of single TFs; it consisted of positive feedbacks among the TFs of the same cluster, and negative interactions among the members of the opposite clusters. Our analyses indicated that the tristable dynamical system of the two-cluster regulatory circuitry is more robust than the genetic circuit of two single TFs.

Biosystems, 2014

One of the fundamental problems in bioinformatics is phylogenetic tree reconstruction, which can ... more One of the fundamental problems in bioinformatics is phylogenetic tree reconstruction, which can be used for classifying living organisms into different taxonomic clades. The classical approach to this problem is based on a marker such as 16S ribosomal RNA. Since evolutionary events like genomic rearrangements are not included in reconstructions of phylogenetic trees based on single genes, much effort has been made to find other characteristics for phylogenetic reconstruction in recent years. With the increasing availability of completely sequenced genomes, gene order can be considered as a new solution for this problem. In the present work, we applied maximal common intervals (MCIs) in two or more genomes to infer their distance and to reconstruct their evolutionary relationship. Additionally, measures based on uncommon segments (UCS's), i.e., those genomic segments which are not detected as part of any of the MCIs, are also used for phylogenetic tree reconstruction. We applied these two types of measures for reconstructing the phylogenetic tree of 63 prokaryotes with known COG (clusters of orthologous groups) families. Similarity between the MCI-based (resp. UCS-based) reconstructed phylogenetic trees and the phylogenetic tree obtained from NCBI taxonomy browser is as high as 93.1% (resp. 94.9%). We show that in the case of this diverse dataset of prokaryotes, tree reconstruction based on MCI and UCS outperforms most of the currently available methods based on gene orders, including breakpoint distance and DCJ. We additionally tested our new measures on a dataset of 13 closely-related bacteria from the genus Prochlorococcus. In this case, distances like rearrangement distance, breakpoint distance and DCJ proved to be useful, while our new measures are still appropriate for phylogenetic reconstruction.

Proteins: Structure, Function and Genetics, 2001

A new, simple method based on information theory is introduced to predict the solvent accessibili... more A new, simple method based on information theory is introduced to predict the solvent accessibility of amino acid residues in various states defined by their different thresholds. Prediction is achieved by the application of information obtained from a single amino acid position or pair-information for a window of seventeen amino acids around the desired residue. Results obtained by pairwise information values are better than results from single amino acids. This reinforces the effect of the local environment on the accessibility of amino acid residues. The prediction accuracy of this method in a jackknife test system for two and three states is better than 70 and 60%, respectively. A comparison of the results with those reported by others involving the same data set also testifies to a better prediction accuracy in our case. Proteins 2001;42:452-459.

PLoS ONE, 2014

Decision making at a cellular level determines different fates for isogenic cells. However, it is... more Decision making at a cellular level determines different fates for isogenic cells. However, it is not yet clear how rational decisions are encoded in the genome, how they are transmitted to their offspring, and whether they evolve and become optimized throughout generations. In this paper, we use a game theoretic approach to explain how rational decisions are made in the presence of cooperators and competitors. Our results suggest the existence of an internal switch that operates as a biased coin. The biased coin is, in fact, a biochemical bistable network of interacting genes that can flip to one of its stable states in response to different environmental stimuli. We present a framework to describe how the positions of attractors in such a gene regulatory network correspond to the behavior of a rational player in a competing environment. We evaluate our model by considering lysis/lysogeny decision making of bacteriophage lambda in E. coli.

Recently in Cyclotron and Nuclear Medicine Department of NRCAM, at Atomic Energy organization of ... more Recently in Cyclotron and Nuclear Medicine Department of NRCAM, at Atomic Energy organization of Iran (AEOI), a system for producing 1-123 via Xe-124 gas target technology, has been constructed and installed. One of the major problems in this system is the highly expensive cost of the enriched Xenon-124 gas. Therefore, saving this gas inside the system is very important. Unfortunately,

Proteins are built from amino acids sequences. For each amino acid one of the three structures, h... more Proteins are built from amino acids sequences. For each amino acid one of the three structures, helix (H), beta strand(S) or coil(C) are considered as protein secondary structures. For many proteins the secondary structure are not known. Protein secondary structure prediction is an important step in three dimensional structure and function determination of proteins. Neural networks are usually implemented directly for estimating emission probabilities in hidden Markov models. In this paper a new combined structure of hidden Markov models and neural networks is applied. We use the predicted structure of neural network as an initial prediction for estimating emission probabilities of amino acids in a hidden Markov model. Using this combined structure we have increased prediction precision of hidden Markov models for protein secondary structure.

The Protein Journal, 2006

The effect of stabilizing and destabilizing salts on the catalytic behavior of ribonuclease A (RN... more The effect of stabilizing and destabilizing salts on the catalytic behavior of ribonuclease A (RNase A) was investigated at pH 7.5 and 25°C, using spectrophotometric, viscometric and molecular dynamic methods. The changes in the distance between N e2 of His 12 and N d1 of His 119 at the catalytic center of RNase A upon the addition of sodium sulfate, sodium hydrogen sulfate and sodium thiocyanate were evaluated by molecular dynamic methods. The compactness and expansion in terms of Stokes radius of RNase A upon the addition of sulfate ions as kosmotropic salts, and thiocyanate ion as a chaotropic salt, were estimated by viscometric measurements. Enzyme activity was measured using cytidine 2¢, 3¢-cyclic monophosphate as a substrate. The results from the measurements of distances between N e2 of His 12 and N d1 of His 119 and Stokes radius suggest (i) that the presence of sulfate ions decreases the distance between the catalytic His residues and increases the globular compactness, and (ii) that there is an expansion of the enzyme surface as well as elongation of the catalytic center in the presence of thiocyanate ion. These findings are in agreement with activity measurements.

The Protein Journal, 2006

The interactions between bilirubin and human serum albumin (HSA) were studied by isothermal titra... more The interactions between bilirubin and human serum albumin (HSA) were studied by isothermal titration calorimetry (ITC) and UV-vis spectrophotometry at 27°C in 100 mM phosphate buffer pH 7.4 containing 1 mM EDTA. The biphasic shape of the HSA-bilirubin binding curve depicted the existence of two bilirubin binding sets on the HSA structure which had distinct binding interactions. Each binding set contained one or more bilirubin binding site. The first binding set at subdomain IIA included one binding site and had a more hydrophobic microenvironment than the other two binding sites in the second bilirubin binding set (subdomain IIIA). With our method of analysis, the calculated dissociation constant of the first binding site is 1.28Â10 )6 M and 4.80Â10 )4 M for the second and third binding sites. Here, the typical Boltzmann's equation was used with a new approach to calculate the dissociation constants as well as the standard free energy changes for the HSA-bilirubin interactions. Interestingly, our calculations obtained using the Wyman binding potential theory confirmed that our analysis method had been correct (especially for the second binding phase). The molar extinction coefficient determined for the first bound bilirubin molecule depicted that the bilirubin molecules (in low concentrations) should interact with the nonpolar microenvironment of the first high affinity binding site. Binding of the bilirubin molecules to the first binding site was endothermic (DH o >0) and occurred through the large increase in the binding entropy established when the hydrophobic bilirubin molecules escaped from their surrounding polar water molecules and into the hydrophobic medium of the first binding site. On the other hand, the calculated molar extinction coefficient illustrated that the microenvironment of the second binding set (especially for the third binding site) was less hydrophobic than the first one but still more hydrophobic than the buffer medium. The binding of the third bilirubin molecule to the HSA molecule was established more through exothermic (electrostatic) interactions.

Proteins: Structure, Function, and Bioinformatics, 2009

tially summation of pairwise electrostatic and Van der Waals interaction energies, bonds, angles ... more tially summation of pairwise electrostatic and Van der Waals interaction energies, bonds, angles and dihedral angles terms. 11-14 In addition, terms such as entropy and solvent effect are implicitly included. Although physical energy function is widely used in molecular dynamic simulation of proteins, these functions have been out of favor in protein structure prediction because of their greater computational costs. To reduce computational complexity of the protein folding problem, knowledge-based or empirical mean force potential is widely used. The structure of folded proteins reflects the energy of the interaction of all their components, including all enthalpic and entropic contributions, as well as solvent effects.

Proteins: Structure, Function, and Bioinformatics, 2012

Mitochondrion, 2013

Advances in organelle interactomics have led to new insights into organelle functions. In this st... more Advances in organelle interactomics have led to new insights into organelle functions. In this study, we considered the common mitochondrial PIN of four evolutionarily distant eukaryotic species, namely Homo sapiens, Mus musculus, Drosophila melanogaster and Caenorhabditis elegans. By comparative interactomics analysis of mitochondrial PINs in these organisms, five conserved modules were identified. Modules comprise the main mitochondrial tasks, including proteins involved in translation process, mitochondrial import inner membrane proteins, TCA cycle enzymes, mitochondrial electron transport chain, and metabolic enzymes. Furthermore, we reemphasize that subgraphs of network, i.e., motifs and themes, may represent evolutionarily conserved topological units which are biologically significant.

Journal of Theoretical Biology, 2011

Gene expression is the main cause for the existence of various phenotypes. Through this procedure... more Gene expression is the main cause for the existence of various phenotypes. Through this procedure, the information stored in DNA rises to the phenotype. Essentially, gene expression is dependent upon the successful binding of transcription factors (TFs) -a specific type of proteins -to explicit positions in its upstream, TF binding sites (TFBSs). Unfortunately, finding these TFBSs is costly and laborious; therefore, discovering TFBSs computationally is a significant problem that many researches endeavor to solve. In this paper, a new TFBS discovery method is presented by considering known biological facts about TFBSs. The input to this method includes sequences with arbitrary lengths and the output comprises positions that tend to be TFBS. Through the application of previous methods along with a method that focuses on biological and simulated datasets, it is shown that this method achieves higher accuracy in discovering TFBSs.

Journal of Biological Chemistry, 2007

The firefly bioluminescence reaction, which uses luciferin, Mg-ATP, and molecular oxygen to yield... more The firefly bioluminescence reaction, which uses luciferin, Mg-ATP, and molecular oxygen to yield an electronically excited oxyluciferin, is carried out by luciferase and visible light is emitted. The bioluminescence color of firefly luciferases is determined by the luciferase structure and assay conditions. Among different beetle luciferases, those from Phrixothrix railroad worm emit either yellow or red bioluminescence colors. Sequence alignment analysis shows that the red-emitter luciferase from Phrixothrix hirtus has an additional Arg residue at 353, which is absent in firefly luciferases. We report here the construction and purification of a mutant at residue Arg(356), which is not conserved in beetle luciferases. By insertion of an additional residue (Arg(356)) using site-specific insertion mutagenesis in a green-emitter luciferase (Lampyris turkestanicus) the color of emitted light was changed to red and the optimum temperature of activity was also increased. Insertion of this Arg in an important flexible loop showed changes of the bioluminescence color and the luciferase reaction took place with relatively retention of its basic kinetic properties such as Km and relative activity. Comparison of native and mutant luciferases using homology modeling reveals a significant conformational change of the flexible loop in the red mutant. Movement of flexible loop brought about a new ionic interaction concomitant with a change in polarity of the emitter site, thereby leading to red emission. It is worthwhile to note that the increased optimum temperature and emission of red light might make mutant luciferase a suitable reporter for the study of gene expression and bioluminescence imaging.

PLoS ONE, 2014

Decision making at a cellular level determines different fates for isogenic cells. However, it is... more Decision making at a cellular level determines different fates for isogenic cells. However, it is not yet clear how rational decisions are encoded in the genome, how they are transmitted to their offspring, and whether they evolve and become optimized throughout generations. In this paper, we use a game theoretic approach to explain how rational decisions are made in the presence of cooperators and competitors. Our results suggest the existence of an internal switch that operates as a biased coin. The biased coin is, in fact, a biochemical bistable network of interacting genes that can flip to one of its stable states in response to different environmental stimuli. We present a framework to describe how the positions of attractors in such a gene regulatory network correspond to the behavior of a rational player in a competing environment. We evaluate our model by considering lysis/lysogeny decision making of bacteriophage lambda in E. coli.

Biosystems, 2014

One of the fundamental problems in bioinformatics is phylogenetic tree reconstruction, which can ... more One of the fundamental problems in bioinformatics is phylogenetic tree reconstruction, which can be used for classifying living organisms into different taxonomic clades. The classical approach to this problem is based on a marker such as 16S ribosomal RNA. Since evolutionary events like genomic rearrangements are not included in reconstructions of phylogenetic trees based on single genes, much effort has been made to find other characteristics for phylogenetic reconstruction in recent years. With the increasing availability of completely sequenced genomes, gene order can be considered as a new solution for this problem. In the present work, we applied maximal common intervals (MCIs) in two or more genomes to infer their distance and to reconstruct their evolutionary relationship. Additionally, measures based on uncommon segments (UCS's), i.e., those genomic segments which are not detected as part of any of the MCIs, are also used for phylogenetic tree reconstruction. We applied these two types of measures for reconstructing the phylogenetic tree of 63 prokaryotes with known COG (clusters of orthologous groups) families. Similarity between the MCI-based (resp. UCS-based) reconstructed phylogenetic trees and the phylogenetic tree obtained from NCBI taxonomy browser is as high as 93.1% (resp. 94.9%). We show that in the case of this diverse dataset of prokaryotes, tree reconstruction based on MCI and UCS outperforms most of the currently available methods based on gene orders, including breakpoint distance and DCJ. We additionally tested our new measures on a dataset of 13 closely-related bacteria from the genus Prochlorococcus. In this case, distances like rearrangement distance, breakpoint distance and DCJ proved to be useful, while our new measures are still appropriate for phylogenetic reconstruction.

Proteins-structure Function and Bioinformatics, 2009

tially summation of pairwise electrostatic and Van der Waals interaction energies, bonds, angles ... more tially summation of pairwise electrostatic and Van der Waals interaction energies, bonds, angles and dihedral angles terms. 11-14 In addition, terms such as entropy and solvent effect are implicitly included. Although physical energy function is widely used in molecular dynamic simulation of proteins, these functions have been out of favor in protein structure prediction because of their greater computational costs. To reduce computational complexity of the protein folding problem, knowledge-based or empirical mean force potential is widely used. The structure of folded proteins reflects the energy of the interaction of all their components, including all enthalpic and entropic contributions, as well as solvent effects.

Journal of Bioinformatics and Computational Biology

Protein-protein interactions (PPIs) are important for understanding the cellular mechanisms of bi... more Protein-protein interactions (PPIs) are important for understanding the cellular mechanisms of biological functions, but the reliability of PPIs extracted by high-throughput assays is known to be low. To address this, many current methods use multiple evidence from different sources of information to compute reliability scores for such PPIs. However, they often combine the evidence without taking into account the uncertainty of the evidence values, potential dependencies between the information sources used and missing values from some information sources. We propose to formulate the task of scoring PPIs using multiple information sources as a multi-criteria decision making problem that can be solved using data fusion to model potential interactions between the multiple information sources. Using data fusion, the amount of contribution from each information source can be proportioned accordingly to systematically score the reliability of PPIs. Our experimental results showed that th...

ChemInform

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was e... more ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

BMC Bioinformatics

Motivation: Although there are many different algorithms and software tools for aligning sequenci... more Motivation: Although there are many different algorithms and software tools for aligning sequencing reads, fast gapped sequence search is far from solved. Strong interest in fast alignment is best reflected in the $10 6 prize for the Innocentive competition on aligning a collection of reads to a given database of reference genomes. In addition, de novo assembly of next-generation sequencing long reads requires fast overlap-layout-concensus algorithms which depend on fast and accurate alignment. Contribution: We introduce ARYANA, a fast gapped read aligner, developed on the base of BWA indexing infrastructure with a completely new alignment engine that makes it significantly faster than three other aligners: Bowtie2, BWA and SeqAlto, with comparable generality and accuracy. Instead of the time-consuming backtracking procedures for handling mismatches, ARYANA comes with the seed-and-extend algorithmic framework and a significantly improved efficiency by integrating novel algorithmic t...

BMC Systems Biology, 2015

Background: Understanding the mechanisms by which hundreds of diverse cell types develop from a s... more Background: Understanding the mechanisms by which hundreds of diverse cell types develop from a single mammalian zygote has been a central challenge of developmental biology. Conrad H. Waddington, in his metaphoric "epigenetic landscape" visualized the early embryogenesis as a hierarchy of lineage bifurcations. In each bifurcation, a single progenitor cell type produces two different cell lineages. The tristable dynamical systems are used to model the lineage bifurcations. It is also shown that a genetic circuit consisting of two auto-activating transcription factors (TFs) with cross inhibitions can form a tristable dynamical system. Results: We used gene expression profiles of pre-implantation mouse embryos at the single cell resolution to visualize the Waddington landscape of the early embryogenesis. For each lineage bifurcation we identified two clusters of TFsrather than two single TFs as previously proposedthat had opposite expression patterns between the pair of bifurcated cell types. The regulatory circuitry among each pair of TF clusters resembled a genetic circuit of a pair of single TFs; it consisted of positive feedbacks among the TFs of the same cluster, and negative interactions among the members of the opposite clusters. Our analyses indicated that the tristable dynamical system of the two-cluster regulatory circuitry is more robust than the genetic circuit of two single TFs.

Biosystems, 2014

One of the fundamental problems in bioinformatics is phylogenetic tree reconstruction, which can ... more One of the fundamental problems in bioinformatics is phylogenetic tree reconstruction, which can be used for classifying living organisms into different taxonomic clades. The classical approach to this problem is based on a marker such as 16S ribosomal RNA. Since evolutionary events like genomic rearrangements are not included in reconstructions of phylogenetic trees based on single genes, much effort has been made to find other characteristics for phylogenetic reconstruction in recent years. With the increasing availability of completely sequenced genomes, gene order can be considered as a new solution for this problem. In the present work, we applied maximal common intervals (MCIs) in two or more genomes to infer their distance and to reconstruct their evolutionary relationship. Additionally, measures based on uncommon segments (UCS's), i.e., those genomic segments which are not detected as part of any of the MCIs, are also used for phylogenetic tree reconstruction. We applied these two types of measures for reconstructing the phylogenetic tree of 63 prokaryotes with known COG (clusters of orthologous groups) families. Similarity between the MCI-based (resp. UCS-based) reconstructed phylogenetic trees and the phylogenetic tree obtained from NCBI taxonomy browser is as high as 93.1% (resp. 94.9%). We show that in the case of this diverse dataset of prokaryotes, tree reconstruction based on MCI and UCS outperforms most of the currently available methods based on gene orders, including breakpoint distance and DCJ. We additionally tested our new measures on a dataset of 13 closely-related bacteria from the genus Prochlorococcus. In this case, distances like rearrangement distance, breakpoint distance and DCJ proved to be useful, while our new measures are still appropriate for phylogenetic reconstruction.

Proteins: Structure, Function and Genetics, 2001

A new, simple method based on information theory is introduced to predict the solvent accessibili... more A new, simple method based on information theory is introduced to predict the solvent accessibility of amino acid residues in various states defined by their different thresholds. Prediction is achieved by the application of information obtained from a single amino acid position or pair-information for a window of seventeen amino acids around the desired residue. Results obtained by pairwise information values are better than results from single amino acids. This reinforces the effect of the local environment on the accessibility of amino acid residues. The prediction accuracy of this method in a jackknife test system for two and three states is better than 70 and 60%, respectively. A comparison of the results with those reported by others involving the same data set also testifies to a better prediction accuracy in our case. Proteins 2001;42:452-459.

PLoS ONE, 2014

Decision making at a cellular level determines different fates for isogenic cells. However, it is... more Decision making at a cellular level determines different fates for isogenic cells. However, it is not yet clear how rational decisions are encoded in the genome, how they are transmitted to their offspring, and whether they evolve and become optimized throughout generations. In this paper, we use a game theoretic approach to explain how rational decisions are made in the presence of cooperators and competitors. Our results suggest the existence of an internal switch that operates as a biased coin. The biased coin is, in fact, a biochemical bistable network of interacting genes that can flip to one of its stable states in response to different environmental stimuli. We present a framework to describe how the positions of attractors in such a gene regulatory network correspond to the behavior of a rational player in a competing environment. We evaluate our model by considering lysis/lysogeny decision making of bacteriophage lambda in E. coli.

Recently in Cyclotron and Nuclear Medicine Department of NRCAM, at Atomic Energy organization of ... more Recently in Cyclotron and Nuclear Medicine Department of NRCAM, at Atomic Energy organization of Iran (AEOI), a system for producing 1-123 via Xe-124 gas target technology, has been constructed and installed. One of the major problems in this system is the highly expensive cost of the enriched Xenon-124 gas. Therefore, saving this gas inside the system is very important. Unfortunately,

Proteins are built from amino acids sequences. For each amino acid one of the three structures, h... more Proteins are built from amino acids sequences. For each amino acid one of the three structures, helix (H), beta strand(S) or coil(C) are considered as protein secondary structures. For many proteins the secondary structure are not known. Protein secondary structure prediction is an important step in three dimensional structure and function determination of proteins. Neural networks are usually implemented directly for estimating emission probabilities in hidden Markov models. In this paper a new combined structure of hidden Markov models and neural networks is applied. We use the predicted structure of neural network as an initial prediction for estimating emission probabilities of amino acids in a hidden Markov model. Using this combined structure we have increased prediction precision of hidden Markov models for protein secondary structure.

The Protein Journal, 2006

The effect of stabilizing and destabilizing salts on the catalytic behavior of ribonuclease A (RN... more The effect of stabilizing and destabilizing salts on the catalytic behavior of ribonuclease A (RNase A) was investigated at pH 7.5 and 25°C, using spectrophotometric, viscometric and molecular dynamic methods. The changes in the distance between N e2 of His 12 and N d1 of His 119 at the catalytic center of RNase A upon the addition of sodium sulfate, sodium hydrogen sulfate and sodium thiocyanate were evaluated by molecular dynamic methods. The compactness and expansion in terms of Stokes radius of RNase A upon the addition of sulfate ions as kosmotropic salts, and thiocyanate ion as a chaotropic salt, were estimated by viscometric measurements. Enzyme activity was measured using cytidine 2¢, 3¢-cyclic monophosphate as a substrate. The results from the measurements of distances between N e2 of His 12 and N d1 of His 119 and Stokes radius suggest (i) that the presence of sulfate ions decreases the distance between the catalytic His residues and increases the globular compactness, and (ii) that there is an expansion of the enzyme surface as well as elongation of the catalytic center in the presence of thiocyanate ion. These findings are in agreement with activity measurements.

The Protein Journal, 2006

The interactions between bilirubin and human serum albumin (HSA) were studied by isothermal titra... more The interactions between bilirubin and human serum albumin (HSA) were studied by isothermal titration calorimetry (ITC) and UV-vis spectrophotometry at 27°C in 100 mM phosphate buffer pH 7.4 containing 1 mM EDTA. The biphasic shape of the HSA-bilirubin binding curve depicted the existence of two bilirubin binding sets on the HSA structure which had distinct binding interactions. Each binding set contained one or more bilirubin binding site. The first binding set at subdomain IIA included one binding site and had a more hydrophobic microenvironment than the other two binding sites in the second bilirubin binding set (subdomain IIIA). With our method of analysis, the calculated dissociation constant of the first binding site is 1.28Â10 )6 M and 4.80Â10 )4 M for the second and third binding sites. Here, the typical Boltzmann's equation was used with a new approach to calculate the dissociation constants as well as the standard free energy changes for the HSA-bilirubin interactions. Interestingly, our calculations obtained using the Wyman binding potential theory confirmed that our analysis method had been correct (especially for the second binding phase). The molar extinction coefficient determined for the first bound bilirubin molecule depicted that the bilirubin molecules (in low concentrations) should interact with the nonpolar microenvironment of the first high affinity binding site. Binding of the bilirubin molecules to the first binding site was endothermic (DH o >0) and occurred through the large increase in the binding entropy established when the hydrophobic bilirubin molecules escaped from their surrounding polar water molecules and into the hydrophobic medium of the first binding site. On the other hand, the calculated molar extinction coefficient illustrated that the microenvironment of the second binding set (especially for the third binding site) was less hydrophobic than the first one but still more hydrophobic than the buffer medium. The binding of the third bilirubin molecule to the HSA molecule was established more through exothermic (electrostatic) interactions.

Proteins: Structure, Function, and Bioinformatics, 2009

tially summation of pairwise electrostatic and Van der Waals interaction energies, bonds, angles ... more tially summation of pairwise electrostatic and Van der Waals interaction energies, bonds, angles and dihedral angles terms. 11-14 In addition, terms such as entropy and solvent effect are implicitly included. Although physical energy function is widely used in molecular dynamic simulation of proteins, these functions have been out of favor in protein structure prediction because of their greater computational costs. To reduce computational complexity of the protein folding problem, knowledge-based or empirical mean force potential is widely used. The structure of folded proteins reflects the energy of the interaction of all their components, including all enthalpic and entropic contributions, as well as solvent effects.

Proteins: Structure, Function, and Bioinformatics, 2012

Mitochondrion, 2013

Advances in organelle interactomics have led to new insights into organelle functions. In this st... more Advances in organelle interactomics have led to new insights into organelle functions. In this study, we considered the common mitochondrial PIN of four evolutionarily distant eukaryotic species, namely Homo sapiens, Mus musculus, Drosophila melanogaster and Caenorhabditis elegans. By comparative interactomics analysis of mitochondrial PINs in these organisms, five conserved modules were identified. Modules comprise the main mitochondrial tasks, including proteins involved in translation process, mitochondrial import inner membrane proteins, TCA cycle enzymes, mitochondrial electron transport chain, and metabolic enzymes. Furthermore, we reemphasize that subgraphs of network, i.e., motifs and themes, may represent evolutionarily conserved topological units which are biologically significant.

Journal of Theoretical Biology, 2011

Gene expression is the main cause for the existence of various phenotypes. Through this procedure... more Gene expression is the main cause for the existence of various phenotypes. Through this procedure, the information stored in DNA rises to the phenotype. Essentially, gene expression is dependent upon the successful binding of transcription factors (TFs) -a specific type of proteins -to explicit positions in its upstream, TF binding sites (TFBSs). Unfortunately, finding these TFBSs is costly and laborious; therefore, discovering TFBSs computationally is a significant problem that many researches endeavor to solve. In this paper, a new TFBS discovery method is presented by considering known biological facts about TFBSs. The input to this method includes sequences with arbitrary lengths and the output comprises positions that tend to be TFBS. Through the application of previous methods along with a method that focuses on biological and simulated datasets, it is shown that this method achieves higher accuracy in discovering TFBSs.

Journal of Biological Chemistry, 2007

The firefly bioluminescence reaction, which uses luciferin, Mg-ATP, and molecular oxygen to yield... more The firefly bioluminescence reaction, which uses luciferin, Mg-ATP, and molecular oxygen to yield an electronically excited oxyluciferin, is carried out by luciferase and visible light is emitted. The bioluminescence color of firefly luciferases is determined by the luciferase structure and assay conditions. Among different beetle luciferases, those from Phrixothrix railroad worm emit either yellow or red bioluminescence colors. Sequence alignment analysis shows that the red-emitter luciferase from Phrixothrix hirtus has an additional Arg residue at 353, which is absent in firefly luciferases. We report here the construction and purification of a mutant at residue Arg(356), which is not conserved in beetle luciferases. By insertion of an additional residue (Arg(356)) using site-specific insertion mutagenesis in a green-emitter luciferase (Lampyris turkestanicus) the color of emitted light was changed to red and the optimum temperature of activity was also increased. Insertion of this Arg in an important flexible loop showed changes of the bioluminescence color and the luciferase reaction took place with relatively retention of its basic kinetic properties such as Km and relative activity. Comparison of native and mutant luciferases using homology modeling reveals a significant conformational change of the flexible loop in the red mutant. Movement of flexible loop brought about a new ionic interaction concomitant with a change in polarity of the emitter site, thereby leading to red emission. It is worthwhile to note that the increased optimum temperature and emission of red light might make mutant luciferase a suitable reporter for the study of gene expression and bioluminescence imaging.