Arnold Emerson - Academia.edu (original) (raw)

Papers by Arnold Emerson

Research paper thumbnail of Picloram binds to the h1 and h4 helices of HSA domain IIIA at drug binding site 2

International Journal of Biological Macromolecules

Research paper thumbnail of Docking and Molecular Dynamics Simulation Revealed the Potential Inhibitory Activity of Amygdalin in Triple-Negative Breast Cancer Therapeutics Targeting the BRCT Domain of BARD1 Receptor

Research paper thumbnail of Investigating the binding affinity of andrographolide against human SARS-CoV-2 spike receptor-binding domain through docking and molecular dynamics simulations

Journal of Biomolecular Structure & Dynamics, Feb 10, 2023

Research paper thumbnail of Classification of Anti-HIV Compounds using QSAR Studies

The Acquired Immunodeficiency Syndrome (AIDS) is one the most fatal disorders for which there hav... more The Acquired Immunodeficiency Syndrome (AIDS) is one the most fatal disorders for which there have been no complete or successful chemotherapy yet. The pandemic spread of this disease has prompted an unprecedented scientific clinical effort to understand and propagate ways to combat it. Quantitative Structure–Activity Relationship (QSAR) study has been reportedly used to study topological indices, physiochemical and indicator parameters on a series of HEPT analogues for understanding HIV reverse transcriptase inhibitor activity (Shovanlal Gayen et al, 2004). The aim of their study was to correlate the identified molecular surface properties with the inhibitory activity of HIV-1 RT using QSAR. The docking energies were used to categorize anti-HIV compounds as classified and non classified multiple linear regression models. Results indicate that classified MLR had a better predictability than the non classified models. Thus this method of classification proves to be a good predictabil...

Research paper thumbnail of Breast cancer mutation in GATA3 zinc finger 1 induces conformational changes leading to the closer binding of ZnFn2 with a wrapping architecture

Journal of Biomolecular Structure and Dynamics

Abstract GATA3 is a transcription factor, known to regulate the transcriptional network and sever... more Abstract GATA3 is a transcription factor, known to regulate the transcriptional network and several pathways using two zinc fingers. Its mutation is associated with a higher risk of breast cancer. The molecular mechanisms of these mutations are poorly understood. It recognizes -GATA- sites on the DNA, using its two zinc fingers ZnFn1 and ZnFn2. Mutations in ZnFn2 have been studied in the past and well known but recently ZnFn1 mutations are also being reported very frequently in breast cancer patients and there is very less knowledge available regarding the binding modes and mechanism. Here, we have investigated the structural and functional impact of GATA3 mutation M294K on the DNA-binding property. The structure was obtained and mutation was induced before subjecting it to the molecular docking followed by MD simulation. Our findings indicate that the somatic mutation M294K, reported in the GATA3 gene destabilizes the unbound structure but, when it forms the DNA-complex, its overall structural stability is restored by the wrapping architecture of ZnFn2 around the DNA in the palindromic region, leading to the enhanced kinetic stability. The mutation not only affects the ZnFn1 region alone but also influences the whole complex by inducing the conformational changes in the linker region between the two zinc fingers, bringing the two zinc fingers to closer proximity representing the flexibility in binding sites. Our findings provide a better understanding of ZnFn1 mutations and the possibility of a different strategy to target these genes for their clinical relevance. Communicated by Ramaswamy H. Sarma

Research paper thumbnail of Exploring novel drug targets in fatty acid pathway of Plasmodium falciparum

Journal of Applied Pharmaceutical Science, 2015

The malarial parasite Plasmodium falciparum infects humans and proliferates rapidly inside the ho... more The malarial parasite Plasmodium falciparum infects humans and proliferates rapidly inside the host before its detection. The proliferation step requires a large amount of lipids for membrane synthesis. Thus fatty acid biosynthesis occurring in the apicoplast plays an important role in causing cerebral malaria. In this study, we explored and analyzed these pathways using stoichiometric matrix, elementary flux modes and robustness analysis. Based on the above analysis, the robustness of this pathway diminished as the result of virtual enzyme knock out indicating four key enzymes, 3-oxoacyl-ACP synthase, 3-oxoacyl-ACP synthase, 3-oxoacyl-ACP synthase and Glycerol-3-phosphate o-acyl transferase. Among the four, the first three are existing drug targets. Subsequently, we also found that a combinatorial double knock out of these enzymes predicts further reduction in overall pathway enzyme activity. Thus, we propose multi drug targeting as a better way to treat brain malaria.

Research paper thumbnail of Computational studies on PLK1 delta gene in cancer diseases

Article history: Received on: 14/07/2015 Revised on: 19/08/2015 Accepted on: 07/09/2015 Available... more Article history: Received on: 14/07/2015 Revised on: 19/08/2015 Accepted on: 07/09/2015 Available online: 12/11/2015 Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. Polo-like kinases (Plks) are a family of conserved serine/threonine kinases involved in the regulation of cell cycle progression through G2 and mitosis. One of them being PLK1, it’s over expression leads to a variety of cancers. Plk1 delta, an uncharacterized protein sequence found in UniProt was studied and found to consist of the N-terminal portion of plk1gene. The 3D protein structure of PLK1 delta was modeled and then the predicted structure was validated. Molecular dynamics simulation was performed to find the stability of the protein. The modelled protein was docked to BI 2536, an inhibitor of Plk1 to obtain conformation of least binding energy. The interacting sites between the protein and inhibitor were also analyzed.

Research paper thumbnail of Molecular dynamic study on PTEN frameshift mutations in breast cancer provide c2 domain as a potential biomarker

Journal of Biomolecular Structure and Dynamics

Research paper thumbnail of Construction and analysis of brain networks from different neuroimaging techniques

International Journal of Neuroscience

Research paper thumbnail of Computational investigations on the dynamic binding effect of molecular tweezer CLR01 toward intrinsically disordered HIV‐1 Nef

Biotechnology and Applied Biochemistry

Research paper thumbnail of Oncogenomics and CYP450 Implications in Personalized Cancer Therapy

Current Pharmacogenomics and Personalized Medicine

Background: The Human Genome Project has unleashed the power of genomics in clinical practice as ... more Background: The Human Genome Project has unleashed the power of genomics in clinical practice as a choice of individualized therapy, particularly in cancer treatment. Pharmacogenomics is an interdisciplinary field of genomics that deals with drug response, based on individual genetic makeup. Objective: The main genetic events associated with carcinogenesis activate oncogenes or inactivate tumor-suppressor genes. Therefore, drugs should be specific to inactivate or regulate these mutant genes and their protein products for effective cancer treatment. In this review, we summarize how polymedication decisions in cancer treatments based on the evaluation of cytochrome P450 (CYP450) polymorphisms are applied for pharmacogenetic assessment of anticancer therapy outcomes. Results: However, multiple genetic events linked, inactivating a single mutant gene product, may be insufficient to inhibit tumor progress. Thus, genomics and pharmacogenetics directly influence a patient’s response and a...

Research paper thumbnail of Gene Prioritization in Parkinson's Disease Using Human Protein–Protein Interaction Network

Journal of Computational Biology

Research paper thumbnail of Global and regional connectivity analysis of resting-state function MRI brain images using graph theory in Parkinson’s disease

International Journal of Neuroscience

Research paper thumbnail of Dynamic conformational flexibility and molecular interactions of intrinsically disordered proteins

Research paper thumbnail of Docking of HIV-1 with Neem using Autodock in Bioinformatics

Research Journal of Pharmacy and Technology

Research paper thumbnail of Identification of target genes in cancer diseases using protein–protein interaction networks

Network Modeling Analysis in Health Informatics and Bioinformatics

Research paper thumbnail of Study of Residue Closeness Centrality and its Significance in Predicting Cdr Regions in Antibody Light Chains

Research Journal of Pharmacy and Technology

Research paper thumbnail of Understanding contact patterns of protein structures from protein contact map and investigation of unique patterns in the globin‐like folded domains

Journal of Cellular Biochemistry

Research paper thumbnail of Detection of Active Site Residues in Bovine Rhodopsin Using Network Analysis

Trends in Bioinformatics

Topological determinants of the protein structures can be obtained by modeling them as undirected... more Topological determinants of the protein structures can be obtained by modeling them as undirected network, which may relate to functionally important residues. In this study, we aim to analyze the Bovine rhodopsin structure (PDB ID: 1U19A) a GPCR family protein. We modeled the protein structure as, an undirected network and network parameters were calculated and compared with the control random networks. Our findings show that the protein contact network possesses a small world property. The functionally important residues in the protein contact network were identified using residue centrality. The statistical significance of the central residues was determined using the Z-score values of the residue centrality. Results show that residues with high Z-score values are highly conserved, are in close proximity with the ligand and are also situated closer to the centre of mass of the protein.

Research paper thumbnail of An Analysis of Central Residues Between Ligand-Bound and Ligand-Free Protein Structures Based on Network Approach

Protein & Peptide Letters

Research paper thumbnail of Picloram binds to the h1 and h4 helices of HSA domain IIIA at drug binding site 2

International Journal of Biological Macromolecules

Research paper thumbnail of Docking and Molecular Dynamics Simulation Revealed the Potential Inhibitory Activity of Amygdalin in Triple-Negative Breast Cancer Therapeutics Targeting the BRCT Domain of BARD1 Receptor

Research paper thumbnail of Investigating the binding affinity of andrographolide against human SARS-CoV-2 spike receptor-binding domain through docking and molecular dynamics simulations

Journal of Biomolecular Structure & Dynamics, Feb 10, 2023

Research paper thumbnail of Classification of Anti-HIV Compounds using QSAR Studies

The Acquired Immunodeficiency Syndrome (AIDS) is one the most fatal disorders for which there hav... more The Acquired Immunodeficiency Syndrome (AIDS) is one the most fatal disorders for which there have been no complete or successful chemotherapy yet. The pandemic spread of this disease has prompted an unprecedented scientific clinical effort to understand and propagate ways to combat it. Quantitative Structure–Activity Relationship (QSAR) study has been reportedly used to study topological indices, physiochemical and indicator parameters on a series of HEPT analogues for understanding HIV reverse transcriptase inhibitor activity (Shovanlal Gayen et al, 2004). The aim of their study was to correlate the identified molecular surface properties with the inhibitory activity of HIV-1 RT using QSAR. The docking energies were used to categorize anti-HIV compounds as classified and non classified multiple linear regression models. Results indicate that classified MLR had a better predictability than the non classified models. Thus this method of classification proves to be a good predictabil...

Research paper thumbnail of Breast cancer mutation in GATA3 zinc finger 1 induces conformational changes leading to the closer binding of ZnFn2 with a wrapping architecture

Journal of Biomolecular Structure and Dynamics

Abstract GATA3 is a transcription factor, known to regulate the transcriptional network and sever... more Abstract GATA3 is a transcription factor, known to regulate the transcriptional network and several pathways using two zinc fingers. Its mutation is associated with a higher risk of breast cancer. The molecular mechanisms of these mutations are poorly understood. It recognizes -GATA- sites on the DNA, using its two zinc fingers ZnFn1 and ZnFn2. Mutations in ZnFn2 have been studied in the past and well known but recently ZnFn1 mutations are also being reported very frequently in breast cancer patients and there is very less knowledge available regarding the binding modes and mechanism. Here, we have investigated the structural and functional impact of GATA3 mutation M294K on the DNA-binding property. The structure was obtained and mutation was induced before subjecting it to the molecular docking followed by MD simulation. Our findings indicate that the somatic mutation M294K, reported in the GATA3 gene destabilizes the unbound structure but, when it forms the DNA-complex, its overall structural stability is restored by the wrapping architecture of ZnFn2 around the DNA in the palindromic region, leading to the enhanced kinetic stability. The mutation not only affects the ZnFn1 region alone but also influences the whole complex by inducing the conformational changes in the linker region between the two zinc fingers, bringing the two zinc fingers to closer proximity representing the flexibility in binding sites. Our findings provide a better understanding of ZnFn1 mutations and the possibility of a different strategy to target these genes for their clinical relevance. Communicated by Ramaswamy H. Sarma

Research paper thumbnail of Exploring novel drug targets in fatty acid pathway of Plasmodium falciparum

Journal of Applied Pharmaceutical Science, 2015

The malarial parasite Plasmodium falciparum infects humans and proliferates rapidly inside the ho... more The malarial parasite Plasmodium falciparum infects humans and proliferates rapidly inside the host before its detection. The proliferation step requires a large amount of lipids for membrane synthesis. Thus fatty acid biosynthesis occurring in the apicoplast plays an important role in causing cerebral malaria. In this study, we explored and analyzed these pathways using stoichiometric matrix, elementary flux modes and robustness analysis. Based on the above analysis, the robustness of this pathway diminished as the result of virtual enzyme knock out indicating four key enzymes, 3-oxoacyl-ACP synthase, 3-oxoacyl-ACP synthase, 3-oxoacyl-ACP synthase and Glycerol-3-phosphate o-acyl transferase. Among the four, the first three are existing drug targets. Subsequently, we also found that a combinatorial double knock out of these enzymes predicts further reduction in overall pathway enzyme activity. Thus, we propose multi drug targeting as a better way to treat brain malaria.

Research paper thumbnail of Computational studies on PLK1 delta gene in cancer diseases

Article history: Received on: 14/07/2015 Revised on: 19/08/2015 Accepted on: 07/09/2015 Available... more Article history: Received on: 14/07/2015 Revised on: 19/08/2015 Accepted on: 07/09/2015 Available online: 12/11/2015 Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. Polo-like kinases (Plks) are a family of conserved serine/threonine kinases involved in the regulation of cell cycle progression through G2 and mitosis. One of them being PLK1, it’s over expression leads to a variety of cancers. Plk1 delta, an uncharacterized protein sequence found in UniProt was studied and found to consist of the N-terminal portion of plk1gene. The 3D protein structure of PLK1 delta was modeled and then the predicted structure was validated. Molecular dynamics simulation was performed to find the stability of the protein. The modelled protein was docked to BI 2536, an inhibitor of Plk1 to obtain conformation of least binding energy. The interacting sites between the protein and inhibitor were also analyzed.

Research paper thumbnail of Molecular dynamic study on PTEN frameshift mutations in breast cancer provide c2 domain as a potential biomarker

Journal of Biomolecular Structure and Dynamics

Research paper thumbnail of Construction and analysis of brain networks from different neuroimaging techniques

International Journal of Neuroscience

Research paper thumbnail of Computational investigations on the dynamic binding effect of molecular tweezer CLR01 toward intrinsically disordered HIV‐1 Nef

Biotechnology and Applied Biochemistry

Research paper thumbnail of Oncogenomics and CYP450 Implications in Personalized Cancer Therapy

Current Pharmacogenomics and Personalized Medicine

Background: The Human Genome Project has unleashed the power of genomics in clinical practice as ... more Background: The Human Genome Project has unleashed the power of genomics in clinical practice as a choice of individualized therapy, particularly in cancer treatment. Pharmacogenomics is an interdisciplinary field of genomics that deals with drug response, based on individual genetic makeup. Objective: The main genetic events associated with carcinogenesis activate oncogenes or inactivate tumor-suppressor genes. Therefore, drugs should be specific to inactivate or regulate these mutant genes and their protein products for effective cancer treatment. In this review, we summarize how polymedication decisions in cancer treatments based on the evaluation of cytochrome P450 (CYP450) polymorphisms are applied for pharmacogenetic assessment of anticancer therapy outcomes. Results: However, multiple genetic events linked, inactivating a single mutant gene product, may be insufficient to inhibit tumor progress. Thus, genomics and pharmacogenetics directly influence a patient’s response and a...

Research paper thumbnail of Gene Prioritization in Parkinson's Disease Using Human Protein–Protein Interaction Network

Journal of Computational Biology

Research paper thumbnail of Global and regional connectivity analysis of resting-state function MRI brain images using graph theory in Parkinson’s disease

International Journal of Neuroscience

Research paper thumbnail of Dynamic conformational flexibility and molecular interactions of intrinsically disordered proteins

Research paper thumbnail of Docking of HIV-1 with Neem using Autodock in Bioinformatics

Research Journal of Pharmacy and Technology

Research paper thumbnail of Identification of target genes in cancer diseases using protein–protein interaction networks

Network Modeling Analysis in Health Informatics and Bioinformatics

Research paper thumbnail of Study of Residue Closeness Centrality and its Significance in Predicting Cdr Regions in Antibody Light Chains

Research Journal of Pharmacy and Technology

Research paper thumbnail of Understanding contact patterns of protein structures from protein contact map and investigation of unique patterns in the globin‐like folded domains

Journal of Cellular Biochemistry

Research paper thumbnail of Detection of Active Site Residues in Bovine Rhodopsin Using Network Analysis

Trends in Bioinformatics

Topological determinants of the protein structures can be obtained by modeling them as undirected... more Topological determinants of the protein structures can be obtained by modeling them as undirected network, which may relate to functionally important residues. In this study, we aim to analyze the Bovine rhodopsin structure (PDB ID: 1U19A) a GPCR family protein. We modeled the protein structure as, an undirected network and network parameters were calculated and compared with the control random networks. Our findings show that the protein contact network possesses a small world property. The functionally important residues in the protein contact network were identified using residue centrality. The statistical significance of the central residues was determined using the Z-score values of the residue centrality. Results show that residues with high Z-score values are highly conserved, are in close proximity with the ligand and are also situated closer to the centre of mass of the protein.

Research paper thumbnail of An Analysis of Central Residues Between Ligand-Bound and Ligand-Free Protein Structures Based on Network Approach

Protein & Peptide Letters