Recent progress in bioinformatics research has led to the accumulation of huge quantities of biological data at various data sources.
The DNA microarray technology makes it possible to simultaneously analyze large number of genes across different samples.
Clustering of microarray data can reveal the hidden gene expression patterns from large quantities of expression data that in turn
offers tremendous possibilities in functional genomics, comparative genomics, disease diagnosis and drug development. The k-
¬means clustering algorithm is widely used for many practical applications. But the original k-¬means algorithm has several
drawbacks. It is computationally expensive and generates locally optimal solutions based on the random choice of the initial
centroids. Several methods have been proposed in the literature for improving the performance of the k-¬means algorithm. A
meta-heuristic optimization algorithm named harmony search helps find out near-global optimal solutions by searching the entire
solution space. Low clustering accuracy of the existing algorithms limits their use in many crucial applications of life sciences. In
this paper we propose a novel Harmony Search-K means Hybrid (HSKH) algorithm for clustering the gene expression data.
Experimental results show that the proposed algorithm produces clusters with better accuracy in comparison with the existing
The cereal cyst nematodes belonging to Heterodera avenae group
is a complex species consisting of 12 valid species and overlapping
morphological characters make them difficult to be distinguished from one
another. The non coding internal transcribed spacer sequences, ITS1 and ITS2
including 5.8S region of ribosomal DNA (rDNA) has been very useful for the
accurate identification of the species and characterization of molecular genetic
variation within the species of plant parasitic nematodes. In the present study,
sequencing and PCR-RFLP of rDNA has been used to confirm the species identity.
Further it was used to determine the genetic homogeneity of an Indian population
used for whole genome and transcriptome sequencing. The Sequence of ITS1 and
ITS2 including 5.8S showed approximately 99% similarity with the
existing sequences of H. avenae from different countries and
confirmed the species identity. Secondary structure of ITS2 region shows that
the isolates from India, China, Israel and Australian possess more stable
conformational energy than the German strain. Further to characterize the
genetic variation within the population, about 200 individual cysts or females
were analyzed separately by PCR-RFLP of rDNA with five restriction enzymes that
could distinguish H. avenae from other closely related species
within the group. This analysis did not reveal any variation within the
population indicating it is genetically homogeneous and suitable for next
generation sequencing using Illumina platform.
Cereal cyst nematode; Heterodera avenae; PCR-RFLP; genetic homogeneity; ITS-rDNA
Identification of genes that are coexpressed across various tissues and environmental stresses is biologically interesting, since they
may play coordinated role in similar biological processes. Genes with correlated expression patterns can be best identified by using
coexpression network analysis of transcriptome data. In the present study, we analyzed the temporal-spatial coordination of gene
expression in root, leaf and panicle of rice under drought stress and constructed network using WGCNA and Cytoscape. Total of
2199 differentially expressed genes (DEGs) were identified in at least three or more tissues, wherein 88 genes have coordinated
expression profile among all the six tissues under drought stress. These 88 highly coordinated genes were further subjected to
module identification in the coexpression network. Based on chief topological properties we identified 18 hub genes such as ABC
transporter, ATP-binding protein, dehydrin, protein phosphatase 2C, LTPL153 - Protease inhibitor, phosphatidylethanolaminebinding
protein, lactose permease-related, NADP-dependent malic enzyme, etc. Motif enrichment analysis showed the presence of
ABRE cis-elements in the promoters of > 62% of the coordinately expressed genes. Our results suggest that drought stress mediated
upregulated gene expression was coordinated through an ABA-dependent signaling pathway across tissues, at least for the subset
of genes identified in this study, while down regulation appears to be regulated by tissue specific pathways in rice.
Coexpression; Drought stress; Hub gene; Rice; Transcriptome; WGCNA
Heliothis virescens, a polyphagous pest, is one of the most destructive pests of many crops and vegetables. Various insecticides and
pesticides are used by agriculturalists to stop the growth and development of this pest. RNA interference is a new area for the
management of pests/insects by inhibiting the growth related RNAs. This involves the miRNAs identification and its
characterization. In the present study, computational approach is applied to predict putative miRNA candidates along with their
possible target(s) in the Heliothis virescens. A total of 63,662 ESTs were downloaded from dbEST database and processed, trimmed
and masked through EGassembler. The H. virescens contigs database obtained after assembly was now used to find the putative
miRNA candidates by performing a local BLAST with the miRNAs of insects retrieved from miRBase. We have predicted putative
miRNA candidates by homology search against all the reported insect miRNAs. These putative miRNAs candidates were further
validated and filtered by different features. In addition, we have also attempted to predict the putative targets of these filtered
miRNAs, by making use of 3' untranslated regions of mRNAs from B. mori. These miRNAs and their targets in H. virescens will
help in improved understanding of molecular mechanisms of miRNA and development of novel and more precise techniques for
better understanding some post transcriptional gene silencing.
The present study proposed a two-step drug repositioning method based on a protein-protein interaction (PPI) network of two
diseases and the similarity of the drugs prescribed for one of the two. In the proposed method, first, lists of disease related genes
were obtained from a meta-database called Genotator. Then genes shared by a pair of diseases were sought. At the first step of the
method, if a drug having its target(s) in the PPI network, the drug was deemed a repositioning candidate. Because targets of many
drugs are still unknown, the similarities between the prescribed drugs for a specific disease were used to infer repositioning
candidates at the second step. As a first attempt, we applied the proposed method to four different types of diseases: hypertension,
diabetes mellitus, Crohn disease, and autism. Some repositioning candidates were found both at the first and second steps.
Drug repositioning; Disease related genes; Drug target; Drug interaction; Substructure; Side effect; Protein-Protein interaction network
Melanogenesis is a complex multistep process of high molecular weight melanins production by hydroxylation and polymerization
of polyphenols. Melanins have a wide range of applications other than being a sun - protection pigment. Melanogenesis pathway
exists from prokaryotes to eukaryotes. It has evolved over years owing to the fact that the melanin pigment has different roles in
diverse taxa of organisms. Melanin plays a pivotal role in the existence of certain bacteria and fungi whereas in higher organisms it
is a measure of protection against the harmful radiation. We have done a detailed study on various pathways known for melanin
synthesis across species. It was divulged that melanin production is not restricted to tyrosine but there are other secondary
metabolites that synthesize melanin in lower organisms. Furthermore the phylogenetic study of these paths was done to
understand their molecular and cellular development. It has revealed that the melanin synthesis paths have co-evolved in several
groups of organisms. In this study, we also introduce a method for the comparative analysis of a metabolic pathway to study its
evolution based on similarity between enzymatic reactions.
Pathway alignment; Melanogenesis; Tyrosinase; PPO; Laccase; Phylogenetic study; Melanogenesis
Common effluent treatment plant (CETP) for tannery effluent, is the combination of physical, chemical and biological treatment to
facilitate the degradation of industrial waste water. Obviously, the biomass which survives in this extreme environment may have
the ability to utilize the effluent as the sole carbon source for its survival. The ultimate aim of the present investigation is to expose
the microbial diversity in each stage of the CETP through the culture dependent way. Bacterial diversity in the effluent were
analysed through 16S rRNA gene. The community study revealed the dominance of firmicutes and the dominant genus was
Bacillus sp, with variable species diversity. Notably, Putative Bacillus sp, B. firmus and B. licheniformis were observed in all stages of
treatment. The dominant residents were analysed by BProm and TF site scan to prove their uniqueness. This species richness
indicates the capability of liveliness in treatment plant and whose can be exploited for treating the effluent by using modern
CETP - Common Effluent Treatment Plant,
PTIET - Pallavaram Tanners Industrial Effluent Treatment Company Ltd.
CETP; Bacterial community; 16S rRNA; Tannery; Effluent; Firmicutes; Bacillus sp
We investigated the occurrence and genetic diversity of Trichoderma and Hypocrea in Manipur which lies in the Indo-Burma
biodiversity hot spot region. 65 Trichoderma isolates were identified at species level by morphological as well as sequence based
analysis of the internal transcribed spacer region 1 and 4. Altogether 22 different species of Trichoderma and Hypocrea were found,
of which Trichoderma harzianum represent the dominant species. Phylogenetic analysis reveals a clear cut distinction of strains
isolated from various collection sites which further hints the need for detail study of Trichoderma on molecular level.
Bioterrorism is the intended use of pathogenic strains of microbes to widen terror in a population. There is a definite need to
promote research for development of vaccines, therapeutics and diagnostic methods as a part of preparedness to any bioterror
attack in the future. BIRS is an open-access database of collective information on the organisms related to bioterrorism. The
architecture of database utilizes the current open-source technology viz PHP ver 5.3.19, MySQL and IIS server under windows
platform for database designing. Database stores information on literature, generic- information and unique pathways of about 10
microorganisms involved in bioterrorism. This may serve as a collective repository to accelerate the drug discovery and vaccines
designing process against such bioterrorist agents (microbes). The available data has been validated from various online resources
and literature mining in order to provide the user with a comprehensive information system.
The database is freely available at http://www.bioterrorism.biowaves.org
Bioterrorism; unique metabolic pathway; KEGG database; protein; bioterrorism agents
The essential and ubiquitous enzyme fructose bisphosphate aldolase (FBPA) has been a good target for controlling the various
types of infections caused by pathogens and parasites. The parasitic infections of nematodes are the major concern of scientific
community, leading to biochemical characterization of this enzyme. In this work we have developed a small dataset of all types of
FBPA sequences collected from publically available databases (EMBL, NCBI and Uni-Port). The Phylogenetic study shows that
evolutionary relationships among sequences of FBPA are clustered into three main groups. FBPA sequences of Globodera
rostochiensis (FBPA_GR) and Heterodera glycines (FBPA_HG) are placed in group II, sharing the similar evolutionary relationship.
The catalytic mechanism of these enzymes depends upon which class of aldolase, it belongs. The class of enzyme has been
confirmed on the basis of sequences and structural similarity with template structure of class I FBPA. To confirm catalytic
mechanism of above said model structures, the known substrate fructose-1, 6-bisphosphate (FBP) and competitive inhibitor
Mannitol-1, 6 bisphosphate (MBP) were docked at known catalytic site of enzyme of interest. The comparative docking analysis
shows that enzyme-substrate complex is forming similar Schiff base intermediate and conducts C3–C4 bond cleavage by forming
Hydrogen bonding with reaction catalyzing Glu-191, reactive Lys-150, and Schiff base forming Lys-233. On the other hand enzymeinhibitor
noncovalent complex is forming cabinolamine precursor and the proton transfer by the formation of hydrogen bond
between MBP O2 with Glu191 enabling stabilization of cabinolamine transition state, which confirms the similar inhibition
mechanism. Thus we conclude that Plant Parasitic Nematodes (PPNs) have evolutionary and functional relationship with the class
I aldolase enzyme. Hence, FBPA can be targeted to control plant parasitic nematodes.
FBPA; FBPA_HG; 1ZAH_A; FBP; MBP; PPNs; Modeling; Simulation; Docking
Purine nucleoside phosphorylase (PNP; EC: 18.104.22.168) is a key enzyme involved in
the purine salvage pathway. A recent bioinformatic study by Yadav, P. K.
et al. (Bioinformation 2012, 8(14),
664–672) reports PNP as an essential enzyme and potential drug target in
community-acquired methicillin-resistant Staphylococcus aureus
(CA-MRSA). We conducted an analysis using the methodology outlined by the
authors, but were unable to identify PNP as an essential gene product in
CA-MRSA. In addition, the treatment of Staphylococcus aureus
cultures with immucillin-H, a powerful inhibitor of PNP, resulted in the
non-lethal attenuation of growth, suggesting that PNP activity is not essential
for cell viability.
During the course of the anti-infective drug discovery programme, actinomycete strain D25 was recovered from the Thar Desert
soil, Rajasthan, India. Actinomycin type of compound isolated from the strain D25 showed promising activity against multi drug
resistant and extensively drug resistant M. tuberculosis isolates. The present study reports the characteristics and phylogenetic
status of the actinomycete strain D25. Phenotypic and cell wall characteristics revealed that the strain belongs to the genus
Streptomyces. Further 16s rRNA analysis confined the genus Streptomyces with 97% similarity to the closely related species
Streptomyces althioticus KCTC 9752. The 16s rRNA sequence was submitted to GenBank with the accession number JN604533.1.
According to Bossard et al. (2003) strain D25 was found to be a novel species of the genus Streptomyces from Thar Desert soil,
Streptomyces; 16s rRNA; phylogenetic analysis; Thar Desert; antituberculous compound
P-loop NTPases represent a large and highly diverse protein family that is involved in variety of cellular functions. Walker A motif
forms a typical arched conformation, necessary to accommodate the phosphate moiety of the nucleoside tri (or di-) phosphate in Ploop
NTPases. The feature that maintains the ancient architecture of P-loop is unidentified and uncharacterized. Here, using a well
established global network parameter, closeness centrality, we identify that Walker A and its flanking regions (N- and C-terminal)
have high density of globally connected residue positions. We find that closeness centrality of these residue positions are conserved
across common structural core of diverse domains of P-loop NTPase fold. Our results suggest the potential role of globally
connected residues in maintaining the local conformation of P-loop.
Cubilin, (CUBN; also known as intrinsic factor-cobalamin receptor [Homo sapiens Entrez Pubmed ref NM_001081.3; NG_008967.1;
GI: 119606627]), located in the epithelium of intestine and kidney acts as a receptor for intrinsic factor – vitamin B12 complexes.
Mutations in CUBN may play a role in autosomal recessive megaloblastic anemia. The current study investigated the possible role
of CUBN in evolution using phylogenetic testing. A total of 588 BLAST hits were found for the cubilin query sequence and these
hits showed putative conserved domain, CUB superfamily (as on 27th Nov 2012). A first-pass phylogenetic tree was constructed to
identify the taxa which most often contained the CUBN sequences. Following this, we narrowed down the search by manually
deleting sequences which were not CUBN. A repeat phylogenetic analysis of 25 taxa was performed using PhyML, RAxML and
TreeDyn softwares to confirm that CUBN is a conserved protein emphasizing its importance as an extracellular domain and being
present in proteins mostly known to be involved in development in many chordate taxa but not found in prokaryotes, plants and
yeast.. No horizontal gene transfers have been found between different taxa.
Cubilin; CUBN; Amino acid sequences; Phylogeny; Sequence alignment
Relative insulin deficiency, in response to increased metabolic demand (obesity, genetic insulin resistance, pregnancy and aging)
lead to Type2 diabetes. Susceptibility of the type 2 diabetes has a genetic basis, as a subset of people with risk factors (obesity,
Insulin Resistance, pregnancy), develop Type2 Diabetes. We aimed to identify ‘cluster’ of overexpressed genes, underlying
increased beta cell survival in diabetes resistant C57BL/6J ob/ob mice (compared to diabetes susceptible BTBR ob/ob mice). We
used ‘consensus’ overexpression status to identify ‘cluster’ of 11 genes consisting of Aldh18a1, Rfc4, Dynlt3, Prom1, H13, Psen1,
Ssr4, Dad1, Anpep, Fam111a and Plk1. Information (biological processes, molecular functions, cellular components, protein-protein
interactions/associations, gene deletion/knockout/inhibition studies) of all the genes in ‘cluster’ were collected by text mining
using different literature search tools, gene information databases and protein-protein interaction databases. Beta cell specific
function of these genes were also inferred using meta analysis tool of Beta Cell Biology Consortium, by studying the expression
pattern of these genes in microarray studies related to beta-cell stimulation/injury, pancreas development and growth and cell
differentiation. In the ‘clusters’, 6 genes (Dad1, Psen1, Ssr4, Rfc4, H13, Plk1) have a role in cell survival. Only Psen1 was previously
identified to have role in successful beta cell compensation. We advocate these genes to be potentially involved in successful beta
cell compensation and prevent T2D in humans, by conferring protection against diabetogenic insults.
Obesity; Diabetes; metabolic load; Dad1; Psen1
Bovine collagen alpha-1 is a naturally occurring extracellular matrix protein found in tendons and other connective tissues. It plays
a vital role in cell growth, differentiation, attachment, and migration. Recent findings have established that collagen alpha-1 is
involved in osteogenesis imperfecta phenotype in cattle but deep information about other members of this large family is not
available so far. So with a view to finding a new edge and attempt to figure out a correlation among the well attributed Bovine
alpha-1 collagen sequences are executed and analyzed. To do so, comparative analysis among the 28 members of collagen family
has been carried out using Computational tools. Consequently, based on the physico-chemical, secondary structural, functional
and phylogenetic classifications, we have selected collagen 12, 14 and 20 as targets for pathological conditions. These proteins
belong to the FACIT family and significantly showed low glycine and proline content, high instability and aliphatic index.
Moreover, FACIT family collagens contain multiple triple helical domains and being members of the FACIT family, bovine
collagen 12, 14, 20 do not form fibrils by themselves but they are associated to collagen 1 associated fibrils. These collagen
molecules might be crucial candidates to detect and understand the process of matrix remodeling in diseases especially in the arena
of cellular compartments.
Collagen; Extracellular matrix; computational tools
Glucose-6-phosphate dehydrogenase (G6PD) is an enzyme in the pentose phosphate pathway (PPP) that plays an important role in
protecting cells from oxidative damage by producing NADPH and reduced glutathione. G6PD deficiency is considered one of the
most common genetic disorders present in the X chromosome and is the most common of enzymopathic red blood cell disorder.
Angiotensin converting enzyme (ACE) plays an essential role in two physiological systems, one leading to the production of
angiotensin II and the other to the degradation of bradykinin. Most studies focused on an insertion/deletion (I/D) polymorphism
in intron 16 of the ACE gene as a marker for a functional polymorphism. The α2B-adrenergic receptor gene (α2BAR) is a three-amino
acid deletion (12Glu9) polymorphism is located on chromosome 2. (Glu9/Glu9) of this polymorphism has been first time studies in
G6PD individuals. We have selected 39 G6PD deficiency male individuals and PCR was carried out with the I/D polymorphisms.
ACE I/D polymorphism study was carried out in G6PD individuals and showed strong association with DD genotypes and D
alleles OR=39.38, p<0.0001 (95% CI=8.80-176.1) and OR=38.58, p<0.0001 (95% CI=13.21-112.6). Another gene of α2BAR I/D
polymorphism study cannot show any association in DD genotype OR-0.6882,p=0.9388 (95% CI=0.2035-2.327) and with D allele
OR-0.9614,p=0.9388 (95% CI=0.3482-2.653). Our study shows that G6PD deficiency is showing strong association in DD genotype
and D allele of ACE gene and α2BAR gene have not shown any important role and one of the reason could be the low sample size.
G6PD; ACE; α2BAR; Insertion/ Deletion; PCR and Saudi Arabia
4-hydroxypanduratin A is a secondary metabolite of Boesenbergia pandurata Schult. (Fingerroot) plant with various pharmacological
activities such as neuroprotective, potent antioxidant, antibacterial and antifungal. Flaviviral NS2B/NS3 protease activity is
essential for polyprotein processing and viral replication for Japanese Encephalitis Virus (JEV), a major cause of Acute Encephaltis in
Asia. Inhibition of formation of this complex by arresting the binding of NS2B with NS3 would reduce the enzyme's activity to
meager proportions and hence would prevent further viral proliferation. The automated 3D structure of NS2B protein of the JEV
GP78 was predicted based on the sequence-to-structure-to-function paradigm using I-TASSER and the function of NS2B protein
was inferred by matching to other known proteins. The stereochemical quality of predicted structure was checked by PROCHECK.
The antiviral activity of 4-hydroxypanduratin A against NS2B protein as a potential drug has been elucidated in this paper.
Docking simulation analysis showed 4-hydroxypanduratin A as potential inhibitor of NS2B protein/cofactor which is necessary for
NS3 protease activity. 220 derivatives of 4-hydroxypanduratin A were virtually screened with rigid criteria of Lipinski's rule of 5
using Autodock4.2. 4-hydroxypanduratin A was found interacting with target hydrophilic domain in NS2B protein by two Hbonds
(Gly80 and Asp81) with active residues, several hydrophobic interactions, Log P value of 5.6, inhibition constant (Ki) of
51.07nM and lowest binding energy of -9.95Kcal/Mol. Hence, 4-hydroxypanduratin A targeted to Site 2 will have sufficient
profound effect to inhibit protease activity to abrogate viral replication. It could be a promising potential drug candidate for JEV
infections using NS2B Site 2 as a Drug target.
NS2B/NS3 protease; Japanese Encephalitis Virus; Structure prediction; I-TASSER; Molecular Docking; 4- hydroxypanduratin A
DNA methylation, the highly studied epigenetic mechanism which is involved in the regulatory events of various cellular
processes like chromatin structure modifications, chromosomal inactivation, gene expressional patterns, embriyonic developments
and transcriptional modification etc. Various high throughput techniques evolved for direct detection of methylation actions as
well as information across the entire region. However, despite high throughput technological advances in experimental field, the
development of software tools that has been dedicated to the prediction of epigenetic information from specific genome sequences
is warranted. To this end we developed a tissue specific classifier MethFinder based on the frequency of novel sequence patterns
across nine human tissues that was capable of discriminating methylation prone and methylation resistant CpG islands with an
overall accuracy of 93%.
MethFinder is freely available at www.rgcb.res.in/methfinder
DNA methylation; CpG islands; Support Vector Machines (SVM)
Pseudomonas aeruginosa is an opportunistic bacterium known for causing chronic infections in cystic fibrosis and chronic obstructive
pulmonary disease (COPD) patients. Recently, several drug targets in Pseudomonas aeruginosa PAO1 have been reported using
network biology approaches on the basis of essentiality and topology and further ranked on network measures viz. degree and
centrality. Till date no drug/ligand molecule has been reported against this targets.In our work we have identified the ligand
/drug molecules, through Orthologous gene mapping against Bacillus subtilis subsp. subtilis str. 168 and performed modelling and
docking analysis. From the predicted drug targets in PA PAO1, we selected those drug targets which show statistically significant
orthology with a model organism and whose orthologs are present in all the selected drug targets of PA PAO1.Modeling of their
structure has been done using I-Tasser web server. Orthologous gene mapping has been performed using Cluster of Orthologs
(COGs) and based on orthology; drugs available for Bacillus sp. have been docked with PA PAO1 protein drug targets using
MoleGro virtual docker version 4.0.2.Orthologous gene for PA3168 gyrA is BS gyrAfound in Bacillus subtilis subsp. subtilis str. 168.
The drugs cited for Bacillus sp. have been docked with PA genes and energy analyses have been made. Based on Orthologous gene
mapping andin-silico studies, Nalidixic acid is reported as an effective drug against PA3168 gyrA for the treatment of CF and
Pseudomonas aeruginosa; CF; COPD; In-silico; MoleGro virtual docker; Orthology; LigandScout; Nalidixic Acid; Ciprofloxacin; Novobiocin; Norvaline
Adefovir is an adenosine analogue approved by the Food and Drug Administration for the treatment of chronic hepatitis B.
Mutations occurring in the hepatitis B virus (HBV) reverse transcriptase (rt) domains are shown to confer resistance to antiviral
drugs. The role of the rtI233V mutation and adefovir resistance remains contradictory. In this study, it was attempted to evaluate
the impact of putative rtI233V substitution on adefovir action by homology modeling and docking studies. The HBVrt nucleotide
sequence containing rtI233V mutation was obtained from the treatment-naive chronic hepatitis B subject. The three dimensional
model of HBV polymerase/rt was constructed using the HIV-1rt template (PDB code: 1RTD A) and the model was evaluated by
the Ramachandran plot. Autodock was employed to dock the HBV polymerase/rt and adefovir. The modelled structure showed
the amino acid rtI233 to be located away from the drug interactory site. The substitution of isoleucine to valine did not appear to
affect the catalytic sites of the protein. In addition, it does not alter the conformation of bent structure formed by residues 235 to 240
that stabilizes the binding of dNTPs. Therefore, it was predicted that rtI233V substitution may not independently affect the
antiviral action of adefovir and incoming dNTP binding.
Hepatitis B virus; Adefovir; Mutation; Homology model; Docking; Drug resistance
Human matrix metalloproteinase-8 (hMMP-8) plays a important role in the progression of colorectal cancer, metastasis, multiple
sclerosis and rheumetoid arthritis. Extensive MD-simulation of the PDB and solvated structures of hMMP-8 has revealed the
presence of few conserved water molecules around the catalytic and structural zinc (ZnC and ZnS) ions. The coordination of two
conserved water molecules (W and WS) to ZnS and the H-bonding interaction of WS to S151 have indicated the plausible involvement
of that metal ion in the catalytic process. Beside this the coupling of ZnC and ZnS metal ions (ZnC – WH (W1)…..W2 ….H162 - ZnS)
through two conserved hydrophilic centers (occupied by water molecules) may also provide some rational on the recognition of
two zinc ions which were separated by ~13 Å in their X-ray structures. This unique recognition of both the Zn+2 ions in the enzyme
through conserved water molecules may be implemented/ exploited for the design of antiproteolytic agent using water mimic
drug design protocol.
Matrix Metalloproteinase; MD simulation; Zn ions; Catalytic mechanism
Protein flexibility is useful in structural and functional aspect of proteins. We have analyzed the local primary protein sequence
features that in combination can predict the B-value of amino acid residues directly from the protein sequence. We have also
analyzed the distribution of B-value in different regions of protein three dimensional structures. On an average, the normalized Bvalue
decreases by 0.1055 with every 0.5Å increase in the distance of the residue from protein surface. The residues in the loop
regions have higher B-values as compared to the residues present in other regular secondary structural elements. Buried residues
which are present in the protein core are more rigid (lower B-values) than the residues present on the protein surface. Similarly, the
hydrophobic residues which tend to be present in the protein core have lower average B-value than the polar residues. Finally, we
have proposed the method based on Support Vector Regression (SVR) to predict the B-value from protein primary sequence. Our
result shows that, the SVR model achieved the correlation coefficient of 0.47 which is comparable to existing methods.
B-value; Protein flexibility; Support Vector Regression; Sliding window approach; Protein dynamics
We propose that the DNA within the chromatin behaves as a dynamic combinatorial library capable of forming novel structures by
reversible processes. We also hypothesize that states within the library may be linked via quantum tunneling. RNA polymerase
then could scan these states and the system decoheres to the “appropriate” state. Two ways of sustaining quantum coherence at
relevant time scales could be possible, first, screening: the quantum system can be kept isolated from its decohering environment,
second, the existence of decoherence free subspaces .We discuss the role of superconductivity in context of avoiding decoherence in
context of our hypothesis.
Tautomeric; Decoherence; Superconductivity