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Objective: To assess the prevalence of temporomandibular ailments and their severity in dental undergraduate students. Study Design: Cross sectional study Place and Duration of Study: Department of Orthodontics, Bacha Khan Medical... more
Objective: To assess the prevalence of temporomandibular ailments and their severity in dental undergraduate students. Study Design: Cross sectional study Place and Duration of Study: Department of Orthodontics, Bacha Khan Medical & Dental College, Mardan from1st October 2020 to 31st March 2021. Methodology: Five hundred and fifty dentistry students were enrolled. After ethical approval each student and written permission for participating in this study was taken. A Fonseca questionnaire was used for assessing the temporomandibular ailments. Responses in form of yes, no and sometimes were scored as 10, 0 and 5 points. A score between 0-15 was considered as nil for temporomandibular disorders while 20-40 as mild, 45-65 as moderate and 70-100 as severe. Results: Three hundred and forty-seven students were nil for temporomandibular, 112 were mild, 58 were moderate while 33 were severe. Conclusion: A 37% had temporomandibular disorders in dentistry students with severity common in 6 percent. Keywords: Temporomandibular ailment, Prevalence, Severity
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A Martelella endophytica (M. endophytica) strain YC6887 was previously isolated from the roots of a halophyte, Rosa rugosa, which was sequenced and characterized. The genomic and proteomic analysis showed a carbohydrate-degrading enzyme,... more
A Martelella endophytica (M. endophytica) strain YC6887 was previously isolated from the roots of a halophyte, Rosa rugosa, which was sequenced and characterized. The genomic and proteomic analysis showed a carbohydrate-degrading enzyme, endoglucanase Cel5A which was further characterized. The protein analysis revealed that this endoglucanase belongs to glycosidic hydrolase family 5 (GH5) with catalytic domain. This gene encodes 349-residue polypeptide and shows closest similarity with cellulases of other Martelella species. The protein was purified to homogeneity and shown that it was a 39 kDa protein. The purified recombinant Cel5A endoglucanase exhibited maximum activity at 50 °C and pH 4.5. The enzyme was salt tolerant and retained more than 50% residual activity up to 15% NaCl. The homology model structure of Cel5A displayed that it is stable and compact protein structure consisting of eleven α-helical structures and eight β-sheets. According to the predicted ligand binding site after superimposition with Pseudomonas stutzeri endoglucanase Cel5A (PDB ID: 4LX4), it consisted of five amino acid Asn157, Tyr116, Glu158, Glu270 and Trp303 that may be the expected active site of Cel5A from YC6887. This presented that our strain M. endophytica YC6887 that produces cellulase partially degrade the insoluble polysaccharides into reducing sugars.
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We construct a protein–protein interaction (PPI) targeted drug-likeness dataset and propose a deep molecular generative framework to generate novel drug-likeness molecules from the features of the seed compounds. This framework gains... more
We construct a protein–protein interaction (PPI) targeted drug-likeness dataset and propose a deep molecular generative framework to generate novel drug-likeness molecules from the features of the seed compounds. This framework gains inspiration from published molecular generative models, uses the key features associated with PPI inhibitors as input and develops deep molecular generative models for de novo molecular design of PPI inhibitors. For the first time, quantitative estimation index for compounds targeting PPI was applied to the evaluation of the molecular generation model for de novo design of PPI-targeted compounds. Our results estimated that the generated molecules had better PPI-targeted drug-likeness and drug-likeness. Additionally, our model also exhibits comparable performance to other several state-of-the-art molecule generation models. The generated molecules share chemical space with iPPI-DB inhibitors as demonstrated by chemical space analysis. The peptide charact...
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Background: Incoherent use of antibiotics has led toward resistance in MRSA, becoming multidrug-resistant with a high rate of virulence in the community and hospital settings. Objective: Synergistic anti-MRSA activity was investigated in... more
Background: Incoherent use of antibiotics has led toward resistance in MRSA, becoming multidrug-resistant with a high rate of virulence in the community and hospital settings. Objective: Synergistic anti-MRSA activity was investigated in this study for hybrid material composite spheres of amoxicillin, Ag nanoparticles, and chitosan, which were prepared by one-step synthesis method, and various characterizations were performed. Methods: Antimicrobial-susceptibility assay on MRSA was achieved by disc diffusion and agar dilution techniques, while agar well diffusion was used for hybrid composite spheres. The in vitro and cytotoxicity studies were conducted on the skin abrasion mouse model and MTT assay on RD cell, respectively. Results: All isolates showed resistance to the tested antibiotics except vancomycin. MIC against MRSA showed high resistance with amoxicillin from 4 to 128 mg L-1. The mean diameter of chitosan spheres and Ag nanoparticles was 02 mm and 277 nm, respectively. Mor...
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Spleen tyrosine kinase (SYK) is an essential mediator of immune cell signaling and has been anticipated as a therapeutic target for autoimmune diseases, notably rheumatoid arthritis, allergic rhinitis, asthma, and cancers. Significant... more
Spleen tyrosine kinase (SYK) is an essential mediator of immune cell signaling and has been anticipated as a therapeutic target for autoimmune diseases, notably rheumatoid arthritis, allergic rhinitis, asthma, and cancers. Significant attempts have been undertaken in recent years to develop SYK inhibitors; however, limited success has been achieved due to poor pharmacokinetics and adverse effects of inhibitors. The primary goal of this research was to identify potential inhibitors having high affinity, selectivity based on key molecular interactions, and good drug-like properties than the available inhibitor, fostamatinib. In this study, a 3D-QSAR model was built for SYK based on known inhibitor IC50 values. The best pharmacophore model was then used as a 3D query to screen a drug-like database to retrieve hits with novel chemical scaffolds. The obtained compounds were subjected to binding affinity prediction using the molecular docking approach, and the results were subsequently va...
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Additional file 7. 2D interaction representation of the reference compound and 1URW. Molecular interaction details of the reference compound.
Objective: To assess the prevalence of temporomandibular ailments and their severity in dental undergraduate students. Study Design: Cross sectional study Place and Duration of Study: Department of Orthodontics, Bacha Khan Medical &... more
Objective: To assess the prevalence of temporomandibular ailments and their severity in dental undergraduate students. Study Design: Cross sectional study Place and Duration of Study: Department of Orthodontics, Bacha Khan Medical & Dental College, Mardan from1st October 2020 to 31st March 2021. Methodology: Five hundred and fifty dentistry students were enrolled. After ethical approval each student and written permission for participating in this study was taken. A Fonseca questionnaire was used for assessing the temporomandibular ailments. Responses in form of yes, no and sometimes were scored as 10, 0 and 5 points. A score between 0-15 was considered as nil for temporomandibular disorders while 20-40 as mild, 45-65 as moderate and 70-100 as severe. Results: Three hundred and forty-seven students were nil for temporomandibular, 112 were mild, 58 were moderate while 33 were severe. Conclusion: A 37% had temporomandibular disorders in dentistry students with severity common in 6 per...
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Active sites comparison. Comparison of the active site residues of 4AG8 and 1UMR. (DOCX 13Â kb)
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2D interaction representation of the Hit compound and 1URW. Molecular interaction details of the Hit compound. (DOCX 264Â kb)
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2D interaction representation of the reference compound and 1URW. Molecular interaction details of the reference compound. (DOCX 204Â kb)
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Docking of the co-crystal within the binding pocket of 1URW. Docking of the co-crystal within the binding pocket. Pink is the docked pose and green represents the co-crystal position. (DOCX 142Â kb)
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2D interaction representation of the Hit compound and 4AG8. Detailed molecular interactions of the Hit compound. (DOCX 424Â kb)
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2D interaction representation of the the reference compound and 4AG8. Detailed molecular interactions of the reference compound. (DOCX 420Â kb)
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Cocrystal re-dock results of 4AG8. Overlapping of the co-crystal (cyan) onto the docked pose (orange). The binding pattern was found to be similar. (DOCX 181Â kb)
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Test set assessment. Assessing the test set values for estimated and the experimental activities by Hypo1. (DOCX 18Â kb)
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Additional file 9. Active sites comparison. Comparison of the active site residues of 4AG8 and 1URW.
Objectives: The objectives of the study were to determine the level of non-compliance with long-term glaucoma therapy in patients presenting in glaucoma department of Al-Shifa Trust Eye Hospital and to identify the health-seeking... more
Objectives: The objectives of the study were to determine the level of non-compliance with long-term glaucoma therapy in patients presenting in glaucoma department of Al-Shifa Trust Eye Hospital and to identify the health-seeking predictors affecting it. Methods: A cross-sectional study of 5 months was conducted on glaucoma patients who are taking follow-up visits in glaucoma department for 6 months or more. The level of compliance with glaucoma medication (dependent variable) was assessed through a scale at first and further transformed into binary variable afterward. Chi-square test of independence was used followed by logistic regression to find out the predictors of compliance. Results: A total of 200 patients participated in the study. Majority of them were from urban background (n=125, 62.5%) and were diagnosed with glaucoma 1–5 years (n=104, 52%) back. Almost 16.00% of patients were not giving follow-up on given appointment. Moreover, 10.00% were not taking proper medications...
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Following publication of the original article [1], the authors reported errors in Figure 3, Figure 14a, Figure 18, Figure 19b, Additional file 3 and Additional file 7.
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Drug resistance is a core issue in cancer chemotherapy. A known folate antagonist, methotrexate (MTX) inhibits human dihydrofolate reductase (hDHFR), the enzyme responsible for the catalysis of 7,8-dihydrofolate reduction to... more
Drug resistance is a core issue in cancer chemotherapy. A known folate antagonist, methotrexate (MTX) inhibits human dihydrofolate reductase (hDHFR), the enzyme responsible for the catalysis of 7,8-dihydrofolate reduction to 5,6,7,8-tetrahydrofolate, in biosynthesis and cell proliferation. Structural change in the DHFR enzyme is a significant cause of resistance and the subsequent loss of MTX. In the current study, wild type hDHFR and double mutant (engineered variant) F31R/Q35E (PDB ID: 3EIG) were subject to computational study. Structure-based pharmacophore modeling was carried out for wild type (WT) and mutant (MT) (variant F31R/Q35E) hDHFR structures by generating ten models for each. Two pharmacophore models, WT-pharma and MT-pharma, were selected for further computations, and showed excellent ROC curve quality. Additionally, the selected pharmacophore models were validated by the Guner-Henry decoy test method, which yielded high goodness of fit for WT-hDHFR and MT-hDHFR. Using...
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Enoyl-acyl carrier protein reductase (ENR) catalyzes the last reduction step in the bacterial type II fatty acid biosynthesis cycle. ENRs include FabI, FabL, FabL2, FabK, and FabV. Previously, we reported a unique triclosan (TCL)... more
Enoyl-acyl carrier protein reductase (ENR) catalyzes the last reduction step in the bacterial type II fatty acid biosynthesis cycle. ENRs include FabI, FabL, FabL2, FabK, and FabV. Previously, we reported a unique triclosan (TCL) resistant ENR homolog that was predominant in obligate intracellular pathogenic bacteria and Apicomplexa. Herein, we report the biochemical and structural basis of TCL resistance in this novel ENR. The purified protein revealed NADH-dependent ENR activity and shared similarity to prototypic FabI. Thus, this metagenome-derived ENR was designated FabI2. Unlike other prototypic bacterial ENRs with the YX6K type catalytic domain, FabI2 possessed a unique YX7K type catalytic domain. Computational modeling followed by site-directed mutagenesis revealed that mild resistance (20 µg/ml of minimum inhibitory concentration) of FabI2 to TCL was confined to the relatively less bulky side chain of A128. Substitution of A128 in FabI2 with bulky valine (V128) elevated TCL ...
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Extremophiles, the microorganisms thriving in extreme environments, provide valuable resources for practicing novel biotechnological processes. Pakistan homes a wide spectrum of extreme environments which harbor various biotechnologically... more
Extremophiles, the microorganisms thriving in extreme environments, provide valuable resources for practicing novel biotechnological processes. Pakistan homes a wide spectrum of extreme environments which harbor various biotechnologically significant microorganisms. This review gauges the structural and functional bacterial diversity of several extreme environments, emphasizing their potentials as a source of extremozymes, and in bioleaching, bioremediation, and bioenergy production at regional level. Further, this review highlights a panoramic account of the local natural conservatories of extremophiles. The inadequacies of current fragmental research are discussed with suggestions to quantitatively define the structural and functional diversity of unexplored extreme localities.
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Mechanistically, neurotoxic insults provoke Ca2+-mediated calpain activation, which cleaves the cytoplasmic region of membrane-embedded p35 and produces its truncated form p25. Upon physical interaction, cyclin-dependent kinase 5 (Cdk5)... more
Mechanistically, neurotoxic insults provoke Ca2+-mediated calpain activation, which cleaves the cytoplasmic region of membrane-embedded p35 and produces its truncated form p25. Upon physical interaction, cyclin-dependent kinase 5 (Cdk5) and p25 forms hyperactivated Cdk5/p25 complex and causes severe neuropathological aberrations including hyperphosphorylated tau-mediated neurofibrillary tangles formation, Alzheimer’s symptoms, and neuronal death. Therefore, the inhibition of Cdk5/p25 complex may relieve p-tau-mediated Alzheimer’s pathology. Herein, computational simulations have identified pyrrolidine-2,3-dione derivatives as novel inhibitors of Cdk5/p25 complex. A ligand-based pharmacophore was designed and employed as 3D query to retrieve drug-like molecules from chemical databases. By molecular docking, drug-like molecules obtaining dock score > 67.67 (Goldcore of the reference compound) were identified. Molecular dynamics simulation and binding free energy calculation retriev...
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Breast cancer (BC) is the leading cause of death among women worldwide devoid of effective treatment. It is therefore important to develop agents that can reverse, reduce, or slow the growth of BC. The use of natural products as... more
Breast cancer (BC) is the leading cause of death among women worldwide devoid of effective treatment. It is therefore important to develop agents that can reverse, reduce, or slow the growth of BC. The use of natural products as chemopreventive agents provides enormous advantages. The aim of the current investigation is to determine the efficacy of the phytochemicals against BC along with the approved drugs to screen the most desirable and effective phytocompound. In the current study, 36 phytochemicals have been evaluated against aromatase to identify the potential candidate drug along with the approved drugs employing the Cdocker module accessible on the Discovery Studio (DS) v4.5 and thereafter analysing the stability of the protein ligand complex using GROningen MAchine for Chemical Simulations v5.0.6 (GROMACS). Additionally, these compounds were assessed for the inhibitory features employing the structure-based pharmacophore (SBP). The Cdocker protocol available with the DS has...
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Dihydrofolate reductase (DHFR) is an essential cellular enzyme and thereby catalyzes the reduction of dihydrofolate to tetrahydrofolate (THF). In cancer medication, inhibition of human DHFR (hDHFR) remains a promising strategy, as it... more
Dihydrofolate reductase (DHFR) is an essential cellular enzyme and thereby catalyzes the reduction of dihydrofolate to tetrahydrofolate (THF). In cancer medication, inhibition of human DHFR (hDHFR) remains a promising strategy, as it depletes THF and slows DNA synthesis and cell proliferation. In the current study, ligand-based pharmacophore modeling identified and evaluated the critical chemical features of hDHFR inhibitors. A pharmacophore model (Hypo1) was generated from known inhibitors of DHFR with a correlation coefficient (0.94), root mean square (RMS) deviation (0.99), and total cost value (125.28). Hypo1 was comprised of four chemical features, including two hydrogen bond donors (HDB), one hydrogen bond acceptor (HBA), and one hydrophobic (HYP). Hypo1 was validated using Fischer’s randomization, test set, and decoy set validations, employed as a 3D query in a virtual screening at Maybridge, Chembridge, Asinex, National Cancer Institute (NCI), and Zinc databases. Hypo1-retri...
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Bacterial peptide deformylase (PDF) is an attractive target for developing novel inhibitors against several types of multidrug-resistant bacteria. The objective of the current study is to retrieve potential phytochemicals as prospective... more
Bacterial peptide deformylase (PDF) is an attractive target for developing novel inhibitors against several types of multidrug-resistant bacteria. The objective of the current study is to retrieve potential phytochemicals as prospective drugs against Staphylococcus aureus peptide deformylase (SaPDF). The current study focuses on applying ligand-based pharmacophore model (PharmL) and receptor-based pharmacophore (PharmR) approaches. Utilizing 20 known active compounds, pharmL was built and validated using Fischer’s randomization, test set method and the decoy set method. PharmR was generated from the knowledge imparted by the Interaction Generation protocol implemented on the Discovery Studio (DS) v4.5 and was validated using the decoy set that was employed for pharmL. The selection of pharmR was performed based upon the selectivity score and further utilizing the Pharmacophore Comparison module available on the DS. Subsequently, the validated pharmacophore models were escalated for ...
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Chagas disease is one of the primary causes of heart diseases accounting to 50,000 lives annually and is listed as the neglected tropical disease. Because the currently available therapies have greater toxic effects with higher... more
Chagas disease is one of the primary causes of heart diseases accounting to 50,000 lives annually and is listed as the neglected tropical disease. Because the currently available therapies have greater toxic effects with higher resistance, there is a dire need to develop new drugs to combat the disease. In this pursuit, the 3D QSAR ligand-pharmacophore (pharm 1) and receptor-based pharmacophore (pharm 2) search was initiated to retrieve the candidate compounds from universal natural compounds database. The validated models were allowed to map the universal natural compounds database. The obtained lead candidates were subjected to molecular docking against cysteine protease (PDB code: 1ME3) employing -Cdocker available on the discovery studio. Subsequently, two Hits have satisfied the selection criteria and were escalated to molecular dynamics simulation and binding free energy calculations. These Hits have demonstrated higher dock scores, displayed interactions with the key residues...
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Aromatase inhibitors with an IC50 value ranging from 1.4 to 49.7uM are known to act as antiepileptic drugs besides being potential breast cancer inhibitors. The aim of the present study is to identify novel antiepileptic aromatase... more
Aromatase inhibitors with an IC50 value ranging from 1.4 to 49.7uM are known to act as antiepileptic drugs besides being potential breast cancer inhibitors. The aim of the present study is to identify novel antiepileptic aromatase inhibitors with higher activity exploiting the ligand-based pharmacophore approach utilizing the experimentally known inhibitors. The resultant Hypo1 consists of four features and was further validated by using three different strategies. Hypo1 was allowed to screen different databases to identify lead molecules and were further subjected to Lipinski' Rule of Five and ADMET to establish their drug-like properties. Consequently, the obtained 68-screened molecules were subjected to molecular docking by GOLD. Furthermore, the compounds with the highest dock scores were assessed for molecular interaction. Later, the MD simulation was applied to evaluate the protein backbone stabilities and binding energies adapting GROMACS 5.0.6 and MM/PBSA which was follo...
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Homozygous and/or heterozygous loss of function mutations in the natriuretic peptide receptor B (NPR2) have been reported in causing acromesomelic dysplasia, type Maroteaux with variable clinical features and idiopathic short stature with... more
Homozygous and/or heterozygous loss of function mutations in the natriuretic peptide receptor B (NPR2) have been reported in causing acromesomelic dysplasia, type Maroteaux with variable clinical features and idiopathic short stature with nonspecific skeletal deformities. On the other hand, gain of function mutations in the same gene result in overgrowth disorder suggesting that NPR2 and its ligand, natriuretic peptide precursor C (CNP), are the key players of endochondral bone growth. However, the precise mechanism behind phenotypic variability of the NPR2 mutations is not fully understood so far. In the present study, three consanguineous families of Pakistani origin (A, B, C) with variable phenotypes of acromesomelic dysplasia, type Maroteaux were evaluated at clinical and molecular levels. Linkage analysis followed by Sanger sequencing of the NPR2 gene revealed three homozygous mutations including p.(Leu314 Arg), p.(Arg371*), and p.(Arg1032*) in family A, B and C, respectively. ...
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Angiogenesis is a process of formation of new blood vessels and is an important criteria demonstrated by cancer cells. Over a period of time, these cancer cells infect the other parts of the healthy body by a process called progression.... more
Angiogenesis is a process of formation of new blood vessels and is an important criteria demonstrated by cancer cells. Over a period of time, these cancer cells infect the other parts of the healthy body by a process called progression. The objective of the present article is to identify a drug molecule that inhibits angiogenesis and progression. In this pursuit, ligand based pharmacophore virtual screening was employed, generating a pharmacophore model, Hypo1 consisting of four features. Furthermore, this Hypo1 was validated recruiting, Fischer's randomization, test set method and decoy set method. Later, Hypo1 was allowed to screen databases such as Maybridge, Chembridge, Asinex and NCI and were further filtered by ADMET filters and Lipinski's Rule of Five. A total of 699 molecules that passed the above criteria, were challenged against 4AG8, an angiogenic drug target employing GOLD v5.2.2. The results rendered by molecular docking, DFT and the MD simulations showed only o...
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Human epidermal growth factor receptors are implicated in several types of cancers characterized by aberrant signal transduction. This family comprises of EGFR (ErbB1), HER2 (ErbB2, HER2/neu), HER3 (ErbB3), and HER4 (ErbB4). Amongst them,... more
Human epidermal growth factor receptors are implicated in several types of cancers characterized by aberrant signal transduction. This family comprises of EGFR (ErbB1), HER2 (ErbB2, HER2/neu), HER3 (ErbB3), and HER4 (ErbB4). Amongst them, HER2 is associated with breast cancer and is one of the most valuable targets in addressing the breast cancer incidences. For the current investigation, we have performed 3D-QSAR based pharmacophore search for the identification of potential inhibitors against the kinase domain of HER2 protein. Correspondingly, a pharmacophore model, Hypo1, with four features was generated and was validated employing Fischer's randomization, test set method and the decoy test method. The validated pharmacophore was allowed to screen the colossal natural compounds database (UNPD). Subsequently, the identified 33 compounds were docked into the proteins active site along with the reference after subjecting them to ADMET and Lipinski's Rule of Five (RoF) employ...
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Enoyl-acyl carrier protein reductase (ENR), such as FabI, FabL, FabK and FabV, catalyzes the last reduction step in bacterial type II fatty acid biosynthesis. Previously, we reported metagenome-derived ENR homologs resistant to triclosan... more
Enoyl-acyl carrier protein reductase (ENR), such as FabI, FabL, FabK and FabV, catalyzes the last reduction step in bacterial type II fatty acid biosynthesis. Previously, we reported metagenome-derived ENR homologs resistant to triclosan (TCL) and highly similar to 7-α hydroxysteroid dehydrogenase (7-AHSDH). These homologs are commonly found in Epsilonproteobacteria, a class that contains several human pathogenic bacteria, including the genera and Herein, we report the biochemical and predicted structural basis of TCL resistance in a novel 7-AHSDH-like ENR. The purified protein exhibited NADPH-dependent ENR activity but no 7-AHSDH activity, despite its high homology with 7-AHSDH (69%-96%). Because this ENR was similar to FabL (41%), we propose that this metagenome-derived ENR is referred to as FabL2. Homology modeling, molecular docking, and molecular dynamic simulation analyses revealed the presence of an extrapolated six-amino acid loop specific to FabL2 ENR, which prevented the e...
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Proteins deacetylation by Histone deacetylase 6 (HDAC6) has been shown in various human chronic diseases like neurodegenerative diseases and cancer, and hence is an important therapeutic target. Since, the existing inhibitors have... more
Proteins deacetylation by Histone deacetylase 6 (HDAC6) has been shown in various human chronic diseases like neurodegenerative diseases and cancer, and hence is an important therapeutic target. Since, the existing inhibitors have hydroxamate group, and are not HDAC6-selective, therefore, this study has designed to investigate non-hydroxamate HDAC6 inhibitors. Ligand-based pharmacophore was generated from 26 training set compounds of HDAC6 inhibitors. The statistical parameters of pharmacophore (Hypo1) included lowest total cost of 115.63, highest cost difference of 135.00, lowest RMSD of 0.70 and the highest correlation of 0.98. The pharmacophore was validated by Fischer's Randomization and Test Set validation, and used as screening tool for chemical databases. The screened compounds were filtered by fit value ([Formula: see text]), estimated Inhibitory Concentration (IC[Formula: see text]) ([Formula: see text]), Lipinski's Rule of Five and Absorption, Distribution, Metabol...
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Antibiotic resistance is a defense mechanism, harbored by pathogens to survive under unfavorable conditions. Among several antibiotic resistant microbial consortium, Staphylococcus aureus is one of the most havoc microorganisms.... more
Antibiotic resistance is a defense mechanism, harbored by pathogens to survive under unfavorable conditions. Among several antibiotic resistant microbial consortium, Staphylococcus aureus is one of the most havoc microorganisms. Staphylococcus aureus encodes a unique enzyme 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase (SaHPPK), against which, none of existing antibiotics have been reported. Computational approaches have been instrumental in designing and discovering new drugs for several diseases. The present study highlights the impact of ginger phytochemicals on Staphylococcus aureus SaHPPK. Herein, we have retrieved eight ginger phytochemicals from published literature and investigated their inhibitory interactions with SaHPPK. To authenticate our work, the investigation proceeds considering the known antibiotics alongside the phytochemicals. Molecular docking was performed employing GOLD and CDOCKER. The compounds with the highest dock score from both the docking programm...
Research Interests: Chemistry, Molecular Dynamics Simulation, Medicine, Humans, Staphylococcus aureus, and 14 moreClinical Sciences, Antibiotics, Hydrogen Bonding, Anti-Bacterial Agents, Plant extracts, Catechols, Microbial Sensitivity Tests, Phytochemicals, Ginger, Structure activity Relationship, Diarylheptanoids, Molecular Structure, DOCK, and binding sites
Progeria is a rare genetic disorder characterized by premature aging that eventually leads to death and is noticed globally. Despite alarming conditions, this disease lacks effective medications; however, the farnesyltransferase... more
Progeria is a rare genetic disorder characterized by premature aging that eventually leads to death and is noticed globally. Despite alarming conditions, this disease lacks effective medications; however, the farnesyltransferase inhibitors (FTIs) are a hope in the dark. Therefore, the objective of the present article is to identify new compounds from the databases employing pharmacophore based virtual screening. Utilizing nine training set compounds along with lonafarnib, a common feature pharmacophore was constructed consisting of four features. The validated Hypo1 was subsequently allowed to screen Maybridge, Chembridge, and Asinex databases to retrieve the novel lead candidates, which were then subjected to Lipinski's rule of 5 and ADMET for drug-like assessment. The obtained 3,372 compounds were forwarded to docking simulations and were manually examined for the key interactions with the crucial residues. Two compounds that have demonstrated a higher dock score than the refe...