Papers by Subbiah Parthasarathy
Current Bioinformatics
Background: In biology, the translation of genetic information to its corresponding protein seque... more Background: In biology, the translation of genetic information to its corresponding protein sequences is carried out by using the Universal Genetic Code. Out of all the possible combinations of 20 amino acids, proteins are formed by the possible combinations that occur naturally. This leaves a large number of unknown combinations of protein sequences that includes the Never Born Proteins. A Never Born Protein is a theoretically possible protein that does not occur in nature or may be selected by evolution in future. Objective: In this study, the "GenNBPSeq" online web server is developed to generate Never Born Protein Sequences and to analyze their sequence and structural stability. Methods: The “GenNBPSeq” server is developed based on the Gray Code and Partitioned Gray Code representations of the Universal Genetic Code combined with the novel Toeplitz matrix approach. The sequence and structure analysis is done by various Bioinformatics tools for the sample Never Born Pro...
International Journal of Antimicrobial Agents, 2021
Frontiers in Bioengineering and Biotechnology, 2019
Amino acid repeats play an important role in the structure and function of proteins. Analysis of ... more Amino acid repeats play an important role in the structure and function of proteins. Analysis of long repeats in protein sequences enables one to understand their abundance, structure and function in the protein universe. In the present study, amino acid repeats of length >50 (long repeats) were identified in a non-redundant set of UniProt sequences using the RADAR program. The underlying structures and functions of these long repeats were carried out using the Gene3D for structural domains, Pfam for functional domains and enzyme and non-enzyme functional classification for catalytic and binding of the proteins. From a structural perspective, these long repeats seem to predominantly occur in certain architectures such as sandwich, bundle, barrel, and roll and within these architectures abundant in the superfolds. The lengths of the repeats within each fold are not uniform exhibiting different structures for different functions. We also observed that long repeats are in the domain regions of the family and are involved in the function of the proteins. After grouping based on enzyme and non-enzyme classes, we observed the abundant occurrence of long repeats in specific catalytic and binding of the proteins. In this study, we have analyzed the occurrence of long repeats in the protein sequence universe apart from well-characterized short tandem repeats in sequences and their structures and functions of the proteins at the domain level. The present study suggests that long repeats may play an important role in the structure and function of domains of the proteins.
Current Computer-Aided Drug Design, 2020
Background: Coronary heart disease generally occurs due to cholesterol accumulation in the walls ... more Background: Coronary heart disease generally occurs due to cholesterol accumulation in the walls of the heart arteries. Statins are the most widely used drugs which work by inhibiting the active site of 3-Hydroxy-3-methylglutaryl-CoA reductase (HMGCR) enzyme that is responsible for cholesterol synthesis. A series of atorvastatin analogs with HMGCR inhibition activity have been synthesized experimentally which would be expensive and time-consuming. Methods: In the present study, we employed both the QSAR model and chemical similarity search for identifying novel HMGCR inhibitors for heart-related diseases. To implement this, a 2D QSAR model was developed by correlating the structural properties to their biological activity of a series of atorvastatin analogs reported as HMGCR inhibitors. Then, the chemical similarity search of atorvastatin analogs was performed by using PubChem database search. Results and Discussion: The three-descriptor model of charge (GATS1p), connectivity (SCH-7...
Current computer-aided drug design, Jan 11, 2018
Vortioxetine is a multimodal antidepressant drug with combined effects on SERT as inhibitor, 5-HT... more Vortioxetine is a multimodal antidepressant drug with combined effects on SERT as inhibitor, 5-HT1A as agonist and 5-HT3A as antagonist. Series of vortioxetine analogs have been reported as multi antidepressant compounds and they block serotonin transport into the neuronal cells, activate the postsynaptic 5-HT1A receptors and eliminate the low activity of 5-HT3A receptors. To explore the important properties of vortioxetine analogs involved in antidepressant activity by developing 2D QSAR models. Selections of significant descriptors were performed by least absolute shrinkage and selection operator (LASSO) method and, the multiple linear regression (MLR) method and All Subsets and GA algorithm included in QSARINS software were used for generating QSAR models. Further, the virtual screening was performed based on bioactivity and structure similarity using the PubChem database. The four descriptor model of complementary information content (CIC2), solubility (bcutp3), mass (bcutm8) an...
Current Computer-Aided Drug Design, 2017
BACKGROUND Top five best hit compounds (ZINC59376795, ZINC60175365, ZINC36922620, ZINC39550705 an... more BACKGROUND Top five best hit compounds (ZINC59376795, ZINC60175365, ZINC36922620, ZINC39550705 and ZINC36953975) were obtained through our high throughput virtual screening (HTVS) analysis with resistant 5204-PBP2B (5204 Penicillin Binding Protein 2B) and sensitive R6-PBP2B (R6 Penicillin Binding Protein 2B) proteins of Streptococcus pneumoniae. OBJECTIVE To gain insight in molecular docking and dynamics simulations of these top five best hit compounds with both resistant 5204-PBP2B and sensitive R6-PBP2B targets. METHODS We have employed Glide XP docking and molecular dynamics simulations of these five best hit compounds with 5204-PBP2B and R6-PBP2B targets. The stability analysis has been carried out through DFT, prime-MM/GBSA binding free energy, RMSD, RMSF and Principal Component Analysis. RESULTS The reference drug, penicillin G forms stable complex with sensitive R6-PBP2B protein. Similar stability is observed for the mutant resistant 5204-PBP2B with the top scoring compound ZINC592376795 which implies that this compound may act as an effective potential inhibitor. The compound ZINC59376795 forms a total of five hydrogen bonds with resistant 5204-PBP2B protein of which three are with mutated residues. Similarly, the other four compounds including penicillin G also form hydrogen bonds with mutated residue. The MD simulations and stability analysis of the complexes of wild and mutant forms are evaluated for a trajectory period of 16ns and further MD simulations of ZINC59376795 with resistant 5204-PBP2B and sensitive R6-PBP2B confirmed the stability for 50 ns. CONCLUSION These results suggest that the top five best hit compounds are found to be a promising gateway for the further development of anti-pneumococcal therapeutics.
Trends in Biochemical Sciences, 1998
LOCAL BENDING OF DNA can contribute extensively to the specificity of biological events such as g... more LOCAL BENDING OF DNA can contribute extensively to the specificity of biological events such as gene regulation and packaging 1. In contrast to traditional structural polymorphism (e.g. the B-, A-and Z-DNA structures), bending is a localized micropolymorphism in which the original B-DNA structure is distorted but is not modified extensively. Broadly speaking, the DNA segments that are involved in the protein-induced and/or inherent DNA bending that occurs
Journal of Integrative Bioinformatics, 2020
Amino acid repeats are found to play important roles in both structures and functions of the prot... more Amino acid repeats are found to play important roles in both structures and functions of the proteins. These are commonly found in all kingdoms of life, especially in eukaryotes and a larger fraction of human proteins composed of repeats. Further, the abnormal expansions of shorter repeats cause various diseases to humans. Therefore, the analysis of repeats of the entire human proteome along with functional, mutational and disease information would help to better understand their roles in proteins. To fulfill this need, we developed a web database HPREP (http://bioinfo.bdu.ac.in/hprep) for human proteome repeats using Perl and HTML programming. We identified different categories of well-characterized repeats and domain repeats that are present in the human proteome of UniProtKB/Swiss-Prot by using in-house Perl programming and novel repeats by using the repeat detection T-REKS tool as well as XSTREAM web server. Further, these proteins are annotated with functional, mutational and d...
Biosystems
In this paper, we identify all possible Gray Code and Partitioned Gray Code representations of th... more In this paper, we identify all possible Gray Code and Partitioned Gray Code representations of the Universal Genetic Code for n = 2-bit and 3-bit binary numbers. We analyse the Hamming Distance matrices of all these Gray code and Partitioned Gray Code possibilities for which we obtain the Toeplitz and Partitioned Toeplitz Matrices, respectively. We use this Gray Code and Partitioned Gray Code representations of the Universal Genetic Code combined with the novel Toeplitz matrix approach to generate many Never Born Protein (NBP) Sequences, which exhibit intrinsic structural stability. In general, Never Born Protein sequences may have many potential applications in synthetic biology and opens a new vista in understanding this new subset of proteins for better applications in drug discovery, synthesis of fine chemicals, etc.
Acta Scientiarum. Biological Sciences
Clitoria ternatea L. is a vital ayurvedic herb featured with a wide spectrum of mental health ben... more Clitoria ternatea L. is a vital ayurvedic herb featured with a wide spectrum of mental health benefits. The present study investigates the competence of the plant against depression and to inhibit the membrane efflux protein P-glycoprotein (P-gp) that can regulate and restrict drug permeation into the brain. Antidepressant competence of the aqueous plant extract was assessed by animal despair studies on depression induced female mice models. The P-glycoprotein inhibitory potential of active phytocompounds was evaluated by molecular docking assay and substantiated by a cell line study. The in vivo studies exhibited a significant difference in the immobility time thereby establishing antidepressant activity. The histopathological sections from cortex region of treated brain showed decreased degenerative changes. Ten imperative phytocompounds facilitated docking complexes against P-glycoprotein among which Kaempferol 3-O-(2״,6״-di-O-rhamnopyranosyl) glucopyranoside exhibited a finest d...
Cell Biochemistry and Biophysics
Cytochrome P450 (CYP) 1A and 2B subfamily enzymes are important drug metabolizing enzymes, and ar... more Cytochrome P450 (CYP) 1A and 2B subfamily enzymes are important drug metabolizing enzymes, and are highly conserved across species in terms of sequence homology. However, there are major to minor structural and macromolecular differences which provide for species-selectivity and substrate-selectivity. Therefore, species-selectivity of CYP1A and CYP2B subfamily proteins across human, mouse and rat was analyzed using molecular modeling, docking and dynamics simulations when the chiral molecules quinine and quinidine were used as ligands. The three-dimensional structures of 17 proteins belonging to CYP1A and CYP2B subfamilies of mouse and rat were predicted by adopting homology modeling using the available structures of human CYP1A and CYP2B proteins as templates. Molecular docking and dynamics simulations of quinine and quinidine with CYP1A subfamily proteins revealed the existence of species-selectivity across the three species. On the other hand, in the case of CYP2B subfamily proteins, no role for chirality of quinine and quinidine in forming complexes with CYP2B subfamily proteins of the three species was indicated. Our findings reveal the roles of active site amino acid residues of CYP1A and CYP2B subfamily proteins and provide insights into species-selectivity of these enzymes across human, mouse, and rat.
Mol. BioSyst., 2016
Analysis of protein–protein interaction networks of CYP proteins of human, mouse and rat gives in... more Analysis of protein–protein interaction networks of CYP proteins of human, mouse and rat gives insights about functionality and species differences.
Current Bioinformatics, 2013
Journal of Bioinformatics and Computational Biology
Our protein block (PB) sequence database PDB-2-PBv1.0 provides PB sequences and dihedral angles f... more Our protein block (PB) sequence database PDB-2-PBv1.0 provides PB sequences and dihedral angles for 74,297 protein structures comprising of 103,252 protein chains of Protein Data Bank (PDB) as on 2011. Since there are a lot of practical applications of PB and also as the size of PDB database increases, it becomes necessary to provide the PB sequences for all PDB protein structures. The current updated PDB-2-PBv3.0 contains PB sequences for 147,602 PDB structures comprising of 400,355 protein chains as on October 2019. When compared to our previous version PDB-2-PBv1.0, the current PDB-2-PBv3.0 contains 2- and 4-fold increase in the number of protein structures and chains, respectively. Notably, it provides PB information for any protein chain, regardless of the missing atom records of protein structure data in PDB. It includes protein interaction information with DNA and RNA along with their corresponding functional classes from Nucleic Acid Database (NDB) and PDB. Now, the updated ...
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Papers by Subbiah Parthasarathy