BoLA-DQA protein is a highly polymorphic region in MHC class II and plays a key role in immune responses, resistance and susceptibility to infectious diseases, vaccination and production factors. Compared with other species, there are little data on molecular characteristics, structure, phylogeny and evolution of BoLA-DQA. In the present study, some aspects of these subjects and propose practical points based on findings about variations, structure and phylogeny of this locus in cattle was studies. Protein sequences of BoLA-DQA alleles were retrieved from databases. Variation was evaluated by Shannon entropy plot based on alignment of sequences with ClustalW2 algorithm, and Highly Variable Regions (HVRs) were analyzed. Then, tertiary structure of protein by homology modeling approach under certain circumstances, energy minimization and model validation were achieved. Finally, phylogeny, allelic grouping and estimation of evolutionary divergence were done using Maximum Likelihood method. For heuristic search of initial tree, Neighbor-Joining and BioNJ were used for pairwise distance matrix by JTT model and then, Logs with better Likelihood were appointed. Seven HVRs and some semi-variable regions in variation analysis were obtained. The highest variable region was amino acids 90-93. These HVRs were seen in all substructures after homology modeling of BoLA-DQA protein (with 97.5 validity). Besides, alleles were grouped into five clusters by phylogenetic analysis. Evolutionary analysis of tree showed that more ancient alleles were *2103 and *2602, and probable newer alleles were *1204, *0302 and *2207. Present study helps in designing effective vaccines against infectious diseases and animal breeding in easy prediction of production factors in cattle.

Recent developments in DNA sequencing and computational algorithms have leading to the discovery of higher value SNPs. In this research, several computational algorithms were used to express the effect of ESRα gene SNPs on protein function in buffalo genome. In this study genomic information of 112 Khuzestani buffaloes that revealed by Affymetrix-90K-SNP-Chip were used. We found two SNPs for ESRα gene. The analysis of these SNPs was performed using Sift, Provean servers. Sift by calculating a zero coefficient, predict that SNPs effects were destructive and effective on protein function. Provean algorithm predict a natural effect by calculating a coefficient of -0.08 for Thr15Ala-SNP and a score of -0.13 for Argenin 43 Histedin-SNP. The SNPs were examined using I-mutant for further investigation of SNPs effects on Protein stability. I-mutant algorithm predict the effect of SNP on protein stability by regression and based on the change in free energy (DDG=-0.49). The result suggestedthat Thronin15Alanin-SNP at 25 °C and pH=7 will reduce the protein stability and Argenin 43 Histedin-SNP, because of its score (DDG=-0.53), has same effect on protein stability. ESRα protein modeling was performed by I-taser server. Validation of the models by Ramachandran plot and Pro-SA server, indicating a deviation in the mutant protein compared to the natural model. Molecular docking in both natural and mutant models indicates no direct changes in the amino acids involved in the interaction. However by side effect and indirectly there is a decrease in ligand binding affinity for the receptor in the mutated model compare to the natural model.

Recent advances in DNA sequencing and computational algorithms revealed the SNPs of highest value. Laboratory study of gene and its alleles is difficult and time consuming. In this study, we used several computational algorithms to demonstrate the effects of gene structure and function of heat shock protein 70 (HSP70) in buffalo. HSP70 is a chaperone molecule that expressed in response to stress. On the other hand, buffalo is one of the resistant animals to heat stress. In this study from Affymetrix 90K SNP chip in 112 Khuzestan buffalo and published sequence information is used for Hindi buffalo. In Khuzestan buffalo dataset, snp was not found, but one snp was recognized in Hindi buffalo. Snp analysis (Methionine/Threonine) was done using SIFT,PROVEAN.SIFT with calculate factor 1 and PROVEAN algorithm with calculate factor 0.33 which showed this mutation or SNP effect is non-destructive and with the normal protein operation. I-mutant algorithm was used to check mutant hsp70 protein stability, and predict SNP impacts on the stability of the protein using regression based on the changes in free energy (DDG=0.47) showed that "met5thr" snp at 25 ºC ,PH=7 decrease the protein stability. Validation of the model by Ramachandran and ProSA Zscore maps indicates a slight deviation in the mutated protein compared to the normal model. Molecular docking and how to hsp70 connect to its ligand adenosine diphosphate (ADP) indicates in both the natural and mutated models that mutation leads to decrease in protein stability and change its structure, which also changes the structure of ligand binding site. But generally in this study the mutation does not show significant and destructive effect on protein structure.

The CD80 protein, a member of the super-family of immunoglobulin, is a transmembrane protein expressed on the surface of the antigen-presenting cells (APC). This protein has two receptors on the surface of T cells (CTLA-4 and CD28), due to the binding of this protein to these receptors, the inhibitory and stimulatory pathway in the T cells begin, respectively. Naturally, CD80 proteins tend to have more binding affinity to CTLA-4 than CD28, and this is a factor in the extinction of T cells in the immune system in order to prevent autoimmunity. The aim of the present study is to create a variant of the CD80 protein that has an increased binding affinity to CD28 to bind to this receptor more strongly and induce more simulate pathways than the wild type of this protein (primary CD80 protein) in T cells. To identify this variant, first, the ancestral sequence was mutated by R software at positions 31 and 92 with amino acids that play an important role in the formation of hydrogen bonds. The R software output sequences were modeled with the SWISS-MODEL server. Then, each output model was docked with the HADDOCK server, and finally, the electrostatic and van der Waals energies between the receptors and the ligands were calculated. Among all the built-in models, the mutated K31Y, R92F has the best electrostatic and van der Waals energies and has the ability to have a much better connection to its CD28 receptor compared to the ancestral type of CD80.

Leishmaniasis is taken into account as a parasitic disease caused by the Leishmania genus. A major challenge of the leishmaniasis is associated with the occurrence of treatment failure after drug treatment. Target identification is a significant factor to reach a drug development. Hence, protein kinases play an important role in drug designing (e.g, LmxMPK and CRK3). This study is developed to predict and assess the three-dimensional structure for E9BJT5 protein in Leishmania and its binding affinity for different calcium channel blockers.

The three-dimensional structure was predicted and assessed for the protein by the I-TASSER and Procheck servers, respectively. In the molecular docking method, interactions between different calcium channel blockers and the predicted model of E9BJT5 were investigated using the Autodock vina in PyRx 0.8 software. Thereafter, the interaction results were analyzed by Chimera software, and thus the stronger potential interactions were identified.

Docking results showed that the lidoflazine and lercanidipine (the values were -8.3 and -7.6 kcal/mol, respectively) were obtained as the top-ranked drugs in the binding to the active site of the protein.

In this study, using in silico approach, the E9BJT5 protein could be a viable target for designing the novel drugs against the Leishmania parasite. The docking results demonstrated that two drugs (i.e., lidoplasin and lercantipine) may be considered as anti-leishmanial drugs. Further studies are recommended to evaluate the interactions between these drugs and the target.

The biosynthesis pathway of fatty acids is one of the important pathways in the body of most organisms that an enzyme Acyl carrier protein (ACP) plays an important role in it. The purpose of this study is phylogenetic and in silico analysis of gene ACP. More analysis indicate that ACP gene has 4 exons, 3 introns and and 2 mRNA in prokaryotes and 13 exons, 12 introns and 9 mRNA in eukaryotes. This protein has target mitochondrial in plant eukaryotes and non-mitochondrial target in prokaryotes and it is not also included of secreted proteins. The results of multiple alignments by T-Coffee server showed that the ACP genes between bacterial species are more protected than plant species. Phylogenetic analysis of ACP proteins in prokaryotes is revealed that except for a cluster, in other case Gram-positive bacteria are in one cluster and gram-negative bacteria are in another cluster. In eukaryotes, different plant species are scattered in different clusters. These results indicated that clustering in eukaryotes are not relate to species. In addition, the study of ACP proteins in eukaryotes and prokaryotes revealed that both eukaryotes and prokaryotes are placed together in some clusters that is due to the similarities of sequences in species. Comparison of the secondary structure of the protein in eukaryotes and prokaryotes showed that the number of alpha and beta sheets in prokaryotes are more than of eukaryotes. Three-dimensional modeling of this protein was done by homology modeling using Swiss Model database in wheat (as representative of eukaryotic) and bacteria Clostridioides difficile 630 (as represented prokaryotes). The best templates were extracted with high similarity from PDB database. To validation of modeled structure and esterochemical analysis, Ramachandran plot was drawn and dihydral angles were calculated. Structural quality evaluation results showed that the proposed models are good quality and stability. The study of protein structure may help to understand protein function and the details of its structure can be useful in studies of the active site of the protein and docking.

Saffron is one of the most expensive spices and natural colors used in various food, pharmaceutical and cosmetic industries. In recent years, a family of enzymes that digest carotenoid substrates into double bonds are identified and introduced in plants. This family is of enzymes Carotenoid Cleavage Dioxygenase (CCD) enzymes. In this study, two isoforms of this gene were cloned and sequenced due to the importance of CCD genes in biosynthesis of apocarotenoids. Bioinformatics analyses including phylogenetic relationships and protein structures were evaluated. 3D modeling of these proteins was done by homologous modeling and using the Swiss Model database after selecting the appropriate pattern. The Ramachandran plot was drawn in order to validate the structure of the 3D model. The results show that the two CCD4a and CCD4b isoforms have both exons and one intron. In silico analysis, the physicochemical properties of CsCCD4a and CsCCD4b proteins also show that the proteins derived from these two isoforms are similar in terms of molecular weight, amino acids, isoelectric points, aliphatic index, instability index and solubility. The results of study of 3D structures resulted in proposal of similar structures for two isoforms. The results of this study can provide valuable information on the behavior and response of CCD4 enzyme in the pathway for synthesis of apricotines in saffron, and these results can be useful in future protein engineering programs.

Nano protein structures can be formed by the intrinsic ability of molecular self-assembly or via intermediates which improve their assembly. Hydrophobicity is the most important factor among the other intrinsic self-assembly factors and the other intermediates such as glutaraldehyde may lead to protein-assembly and nanoparticles formation. In this study, Aggrescan 3D software was employed to investigate protein self-assembly properties. Peroxidase enzyme was selected to form protein nanoparticle, and glutaraldehyde changed it to a nano enzyme.FESEM and DLS analysis represented that the average size of nano enzyme is about 500 nanometers. Comparing biochemical properties of peroxidase enzyme before and after changing into nano, showed that the activity of nano enzyme at 20°C, pH7 has decreased as compared to the monomeric enzyme. Based on homology, the PDB structure of two peroxidase enzyme was identified. Then, the connection between glutaraldehyde and two peroxidase enzymes was detected. Enzyme residues with hydrogen binding connections to glutaraldehyde were also detected by using LigPlot software and the residues in active side of enzyme were determined by COACH server. Glutaraldehyde is connected to residues in active siteof the enzyme. Molecular dynamic Simulation was performed in the time duration of 5 nanoseconds and 30°C and it showed that monomer enzyme and nano enzyme are both stable in this time duration and temperature.

Squalane is an unsaturated triterpene that has wide applications in pharmaceuticals. In this research, the production of squalene and its bioinformatic analysis in four species of unicellular and multicellular eukaryotes and prokaryotes were investigated in order to determine the difference of this gene in eukaryotes and prokaryotes. The results of phylogenetic analysis showed that algae as multicellular eukaryotes, yeast as single-celled eukaryote and bacteria as single-celled prokaryote were placed in one group and plants were placed in a separate group. GC percentage of SQS protein was evaluated by GC Content Calculator, as well as aliphatic index and instability index by protparam. The results showed that the SQS gene is in a range from unstable to stable. The analysis of the presence of signal sequences and the analysis of the detection of the final location of the protein showed that the possibility of transferring the SQS protein to the mitochondria, chloroplast and secretory pathway is very low and it is not among the signal proteins. It was also found in Gymnema sylvestre that this protein has three protected domains. The comparison of the secondary structure of the protein confirmed the existence of alpha sheets. 3D modeling of this protein in plant was done by homology modeling method and using Swiss Model database after selecting a suitable model with high similarity which was extracted from PDB database. In order to validate the structure of the drawn three-dimensional model and stereochemical analysis, the Ramachandran diagram was drawn and the dihedral angles were calculated. The results of structural quality evaluation showed that the proposed models have good quality and stability. The study of the protein structure can help to understand the function of the protein, and studying the details of its structure can be useful in the studies of the active site of the protein and docking.