A pairwise residue contact area-based mean force potential for discrimination of native protein structure

Abstract Background Considering energy function to detect a correct protein fold from incorrect ones is very important for protein structure prediction and protein folding. Knowledge-based mean force potentials are certainly the most popular type of interaction function for protein threading. They are derived from statistical analyses of interacting groups in experimentally determined protein structures. These potentials are developed at the atom or the amino acid level. Based on orientation dependent contact area, a new type of knowledge-based mean force potential has been developed. Results We developed a new approach to calculate a knowledge-based potential of mean-force, using pairwise residue contact area. To test the performance of our approach, we performed it on several decoy sets to measure its ability to discriminate native structure from decoys. This potential has been able to distinguish native structures from the decoys in the most cases. Further, the calculated Z-scores were quite high for all protein datasets. Conclusions This knowledge-based potential of mean force can be used in protein structure prediction, fold recognition, comparative modelling and molecular recognition. The program is available at http://www.bioinf.cs.ipm.ac.ir/softwares/surfield</p

Schizophrenia: The Dark Side of Toxoplasmosis

Toxoplasma gondii is an intracellular parasite that has been associated with several mental disorders. It usually causes an inapparent primary infection. Found worldwide, T. gondii is capable of infecting virtually all warm-blooded animals.1-3Schizophrenia is a neurological disorder characterized with long-term and devastating neuropsychological problems, usually presenting in adolescents or young adults. The disease affects almost 1.1% of the global population including all races and ethnic groups with an equal prevalence in both sexes.1 T. gondii seroprevalence is strongly associated with 12-month generalized anxiety disorder but not with other anxiety, depressive, or alcohol-related disorders. Because of the intracellular nature of some parasites, their treatment and development of new drugs is a major challenge for scientists.4 Recently, the use of nanoparticles and nano-scaffolds has suggested for the treatment of parasitic diseases, although limited research has been done in this regard.5-

A tale of two symmetrical tails: Structural and functional characteristics of palindromes in proteins

<p>Abstract</p> <p>Background</p> <p>It has been previously shown that palindromic sequences are frequently observed in proteins. However, our knowledge about their evolutionary origin and their possible importance is incomplete.</p> <p>Results</p> <p>In this work, we tried to revisit this relatively neglected phenomenon. Several questions are addressed in this work. (1) It is known that there is a large chance of finding a palindrome in low complexity sequences (i.e. sequences with extreme amino acid usage bias). What is the role of sequence complexity in the evolution of palindromic sequences in proteins? (2) Do palindromes coincide with conserved protein sequences? If yes, what are the functions of these conserved segments? (3) In case of conserved palindromes, is it always the case that the whole conserved pattern is also symmetrical? (4) Do palindromic protein sequences form regular secondary structures? (5) Does sequence similarity of the two "sides" of a palindrome imply structural similarity? For the first question, we showed that the complexity of palindromic peptides is significantly lower than randomly generated palindromes. Therefore, one can say that palindromes occur frequently in low complexity protein segments, without necessarily having a defined function or forming a special structure. Nevertheless, this does not rule out the possibility of finding palindromes which play some roles in protein structure and function. In fact, we found several palindromes that overlap with conserved protein Blocks of different functions. However, in many cases we failed to find any symmetry in the conserved regions of corresponding Blocks. Furthermore, to answer the last two questions, the structural characteristics of palindromes were studied. It is shown that palindromes may have a great propensity to form α-helical structures. Finally, we demonstrated that the two sides of a palindrome generally do not show significant structural similarities.</p> <p>Conclusion</p> <p>We suggest that the puzzling abundance of palindromic sequences in proteins is mainly due to their frequent concurrence with low-complexity protein regions, rather than a global role in the protein function. In addition, palindromic sequences show a relatively high tendency to form helices, which might play an important role in the evolution of proteins that contain palindromes. Moreover, reverse similarity in peptides does not necessarily imply significant structural similarity. This observation rules out the importance of palindromes for forming symmetrical structures. Although palindromes frequently overlap with conserved Blocks, we suggest that palindromes overlap with Blocks only by coincidence, rather than being involved with a certain structural fold or protein domain.</p

Insight into molecular characteristics of SARS-CoV-2 spike protein following D614G point mutation, a molecular dynamics study

Undoubtedly, the SARS-CoV-2 has become a major concern for all societies due to its catastrophic effects on public health. In addition, mutations and changes in the structure of the virus make it difficult to design effective treatment. Moreover, the amino acid sequence of a protein is a major factor in the formation of the second and tertiary structure in a protein. Amino acid replacement can have noticeable effects on the folding of a protein, especially if an asymmetric change (substitution of polar residue with non-polar, charged with an uncharged, positive charge with a negative charge, or large residue with small residue) occurs. D614G as a spike mutant of SARS-CoV-2 previously identified as an associated risk factor with a high mortality rate of this virus. Using structural bioinformatics, our group determined that D614G mutation could cause extensive changes in SARS-CoV-2 behavior including the secondary structure, receptor binding pattern, 3D conformation, and stability of it. Communicated by Ramaswamy H. Sarma

In Silico Analysis of Neutralizing Antibody Epitopes on The Hepatitis C Virus Surface Glycoproteins

Objective: Despite of antiviral drugs and successful treatment, an effective vaccine against hepatitis C virus (HCV)infection is still required. Recently, bioinformatic methods same as prediction algorithms, have greatly contributed tothe use of peptides in the design of immunogenic vaccines. Therefore, finding more conserved sites on the surfaceglycoproteins (E1 and E2) of HCV, as major targets to design an effective vaccine against genetically different virusesin each genotype was the goal of the study. Materials and Methods: In this experimental study, 100 entire sequences of E1 and E2 were retrieved from the NCBIwebsite and analyzed in terms of mutations and critical sites by Bioedit 7.7.9, MEGA X software. Furthermore, HCV-1asamples were obtained from some infected people in Iran, and reverse transcriptase-polymerase chain reaction (RTPCR)assay was optimized to amplify their E1 and E2 genes. Moreover, all three-dimensional structures of E1 andE2 downloaded from the PDB database were analyzed by YASARA. In the next step, three interest areas of humoralimmunity in the E2 glycoprotein were evaluated. OSPREY3.0 protein design software was performed to increase theaffinity to neutralizing antibodies in these areas. Results: We found the effective in silico binding affinity of residues in three broadly neutralizing epitopes of E2glycoprotein. First, positions that have substitution capacity were detected in these epitopes. Furthermore, residuesthat have high stability for substitution in these situations were indicated. Then, the mutants with the strongest affinityto neutralize antibodies were predicted. I414M, T416S, I422V, I414M-T416S, and Q412N-I414M-T416S substitutionstheoretically were exhibited as mutants with the best affinity binding. Conclusion: Using an innovative filtration strategy, the residues of E2 epitopes which have the best in silico bindingaffinity to neutralizing antibodies were exhibited and a distinct peptide library platform was designed

Solvent Dependent Activity of Candida Antarctica lipase B and its Correlation with a Regioselective Mono Aza-Michael Addition- Experimental and Molecular Dynamics Simulation Studies

With the aim of gaining understanding of the molecular basis of Candida antarctica lipase B (CALB) catalyzed regioselective mono aza-Michael addition of Benzhydrazide to Diethyl maleat (DEM) we decided to carry out molecular dynamics (MD) simulation studies in parallel with our experimental study. We found a correlation between the activity of CALB and the choice of solvent. Our study showed that solvent affects the performance of the enzyme due to the binding of solvent molecules to the enzyme active site region, and the solvation energy of substrates in the different solvents. We found that CALB is only active in nonpolar solvent (i.e. Hexane), and therefore we investigated the influence of Hexane on the catalytic activity of CALB for the reaction. The results of this study and related experimental validation from our studies have been discussed here

Insight into molecular characteristics of SARS-CoV-2 spike protein following D614G point mutation, a molecular dynamics study

Undoubtedly, the SARS-CoV-2 has become a major concern for all societies due to its catastrophic effects on public health. In addition, mutations and changes in the structure of the virus make it difficult to design effective treatment. Moreover, the amino acid sequence of a protein is a major factor in the formation of the second and tertiary structure in a protein. Amino acid replacement can have noticeable effects on the folding of a protein, especially if an asymmetric change (substitution of polar residue with non-polar, charged with an uncharged, positive charge with a negative charge, or large residue with small residue) occurs. D614G as a spike mutant of SARS-CoV-2 previously identified as an associated risk factor with a high mortality rate of this virus. Using structural bioinformatics, our group determined that D614G mutation could cause extensive changes in SARS-CoV-2 behavior including the secondary structure, receptor binding pattern, 3D conformation, and stability of it

CISPLATIN CHEMORESISTANCE RELATED GENES: A MACHINE LEARNING AND SYSTEMS BIOLOGY ANALYSIS APPROACH

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CentiServer: A Comprehensive Resource, Web-Based Application and R Package for Centrality Analysis.

Various disciplines are trying to solve one of the most noteworthy queries and broadly used concepts in biology, essentiality. Centrality is a primary index and a promising method for identifying essential nodes, particularly in biological networks. The newly created CentiServer is a comprehensive online resource that provides over 110 definitions of different centrality indices, their computational methods, and algorithms in the form of an encyclopedia. In addition, CentiServer allows users to calculate 55 centralities with the help of an interactive web-based application tool and provides a numerical result as a comma separated value (csv) file format or a mapped graphical format as a graph modeling language (GML) file. The standalone version of this application has been developed in the form of an R package. The web-based application (CentiServer) and R package (centiserve) are freely available at http://www.centiserver.org/