LIVIVO - The Search Portal for Life Sciences

zur deutschen Oberfläche wechseln
Advanced search

Search results

Result 1 - 10 of total 43

Search options

  1. Article ; Online: Multiscale MD simulations of wild-type and sickle hemoglobin aggregation.

    Olagunju, Maryam O / Loschwitz, Jennifer / Olubiyi, Olujide O / Strodel, Birgit

    Proteins

    2022  Volume 90, Issue 11, Page(s) 1811–1824

    Abstract: Sickle cell disease is a hemoglobinopathy resulting from a point mutation from glutamate to valine at position six of the β-globin chains of hemoglobin. This mutation gives rise to pathological aggregation of the sickle hemoglobin and, as a result, ... ...

    Abstract Sickle cell disease is a hemoglobinopathy resulting from a point mutation from glutamate to valine at position six of the β-globin chains of hemoglobin. This mutation gives rise to pathological aggregation of the sickle hemoglobin and, as a result, impaired oxygen binding, misshapen and short-lived erythrocytes, and anemia. We aim to understand the structural effects caused by the single Glu6Val mutation leading to protein aggregation. To this end, we perform multiscale molecular dynamics simulations employing atomistic and coarse-grained models of both wild-type and sickle hemoglobin. We analyze the dynamics of hemoglobin monomers and dimers, study the aggregation of wild-type and sickle hemoglobin into decamers, and analyze the protein-protein interactions in the resulting aggregates. We find that the aggregation of sickle hemoglobin is driven by both hydrophobic and electrostatic protein-protein interactions involving the mutation site and surrounding residues, leading to an extended interaction area and thus stable aggregates. The wild-type protein can also self-assemble, which, however, results from isolated interprotein salt bridges that do not yield stable aggregates. This knowledge can be exploited for the development of sickle hemoglobin-aggregation inhibitors.
    MeSH term(s) Glutamates ; Hemoglobin, Sickle/genetics ; Hemoglobin, Sickle/metabolism ; Hemoglobins/chemistry ; Oxygen/metabolism ; Protein Aggregates ; Valine ; beta-Globins
    Chemical Substances Glutamates ; Hemoglobin, Sickle ; Hemoglobins ; Protein Aggregates ; beta-Globins ; Valine (HG18B9YRS7) ; Oxygen (S88TT14065)
    Language English
    Publishing date 2022-05-18
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 806683-8
    ISSN 1097-0134 ; 0887-3585
    ISSN (online) 1097-0134
    ISSN 0887-3585
    DOI 10.1002/prot.26352
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  2. Article ; Online: The Influences of Sulphation, Salt Type, and Salt Concentration on the Structural Heterogeneity of Glycosaminoglycans.

    Samantray, Suman / Olubiyi, Olujide O / Strodel, Birgit

    International journal of molecular sciences

    2021  Volume 22, Issue 21

    Abstract: The increasing recognition of the biochemical importance of glycosaminoglycans (GAGs) has in recent times made them the center of attention of recent research investigations. It became evident that subtle conformational factors play an important role in ... ...

    Abstract The increasing recognition of the biochemical importance of glycosaminoglycans (GAGs) has in recent times made them the center of attention of recent research investigations. It became evident that subtle conformational factors play an important role in determining the relationship between the chemical composition of GAGs and their activity. Therefore, a thorough understanding of their structural flexibility is needed, which is addressed in this work by means of all-atom molecular dynamics (MD) simulations. Four major GAGs with different substitution patterns, namely hyaluronic acid as unsulphated GAG, heparan-6-sulphate, chondroitin-4-sulphate, and chondroitin-6-sulphate, were investigated to elucidate the influence of sulphation on the dynamical features of GAGs. Moreover, the effects of increasing NaCl and KCl concentrations were studied as well. Different structural parameters were determined from the MD simulations, in combination with a presentation of the free energy landscape of the GAG conformations, which allowed us to unravel the conformational fingerprints unique to each GAG. The largest effects on the GAG structures were found for sulphation at position 6, as well as binding of the metal ions in the absence of chloride ions to the carboxylate and sulphate groups, which both increase the GAG conformational flexibility.
    MeSH term(s) Carbohydrate Conformation ; Carbohydrate Sequence ; Chondroitin Sulfates/chemistry ; Chondroitin Sulfates/metabolism ; Glycosaminoglycans/chemistry ; Glycosaminoglycans/metabolism ; Heparitin Sulfate/chemistry ; Heparitin Sulfate/metabolism ; Humans ; Hyaluronic Acid/chemistry ; Hyaluronic Acid/metabolism ; Hydrogen Bonding ; Hydrophobic and Hydrophilic Interactions ; Molecular Dynamics Simulation ; Molecular Structure ; Potassium Chloride/chemistry ; Sodium Chloride/chemistry ; Sulfates/chemistry
    Chemical Substances Glycosaminoglycans ; Sulfates ; Sodium Chloride (451W47IQ8X) ; Potassium Chloride (660YQ98I10) ; Hyaluronic Acid (9004-61-9) ; Chondroitin Sulfates (9007-28-7) ; Heparitin Sulfate (9050-30-0)
    Language English
    Publishing date 2021-10-26
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms222111529
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  3. Article ; Online: The Influences of Sulphation, Salt Type, and Salt Concentration on the Structural Heterogeneity of Glycosaminoglycans

    Suman Samantray / Olujide O. Olubiyi / Birgit Strodel

    International Journal of Molecular Sciences, Vol 22, Iss 11529, p

    2021  Volume 11529

    Abstract: The increasing recognition of the biochemical importance of glycosaminoglycans (GAGs) has in recent times made them the center of attention of recent research investigations. It became evident that subtle conformational factors play an important role in ... ...

    Abstract The increasing recognition of the biochemical importance of glycosaminoglycans (GAGs) has in recent times made them the center of attention of recent research investigations. It became evident that subtle conformational factors play an important role in determining the relationship between the chemical composition of GAGs and their activity. Therefore, a thorough understanding of their structural flexibility is needed, which is addressed in this work by means of all-atom molecular dynamics (MD) simulations. Four major GAGs with different substitution patterns, namely hyaluronic acid as unsulphated GAG, heparan-6-sulphate, chondroitin-4-sulphate, and chondroitin-6-sulphate, were investigated to elucidate the influence of sulphation on the dynamical features of GAGs. Moreover, the effects of increasing NaCl and KCl concentrations were studied as well. Different structural parameters were determined from the MD simulations, in combination with a presentation of the free energy landscape of the GAG conformations, which allowed us to unravel the conformational fingerprints unique to each GAG. The largest effects on the GAG structures were found for sulphation at position 6, as well as binding of the metal ions in the absence of chloride ions to the carboxylate and sulphate groups, which both increase the GAG conformational flexibility.
    Keywords glycosaminoglycans ; sulphation ; GAG–cation interactions ; conformational flexibility ; molecular dynamics simulations ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
    Subject code 540
    Language English
    Publishing date 2021-10-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    More links

    Kategorien

  4. Article ; Online: Dataset of AMBER force field parameters of drugs, natural products and steroids for simulations using GROMACS.

    Loschwitz, Jennifer / Jäckering, Anna / Keutmann, Monika / Olagunju, Maryam / Olubiyi, Olujide O / Strodel, Birgit

    Data in brief

    2021  Volume 35, Page(s) 106948

    Abstract: We provide general AMBER force field (GAFF) parameters for 160 organic molecules including drugs, natural products, and steroids, which can be employed without further processing in molecular dynamics (MD) simulations using GROMACS. We determined these ... ...

    Abstract We provide general AMBER force field (GAFF) parameters for 160 organic molecules including drugs, natural products, and steroids, which can be employed without further processing in molecular dynamics (MD) simulations using GROMACS. We determined these parameters based on quantum mechanical (QM) calculations involving geometry optimization at the HF6-31G* level of theory. For each molecule we provide a coordinate file of the three-dimensional molecular structure, the topology and the parameter file. The applicability of these parameters was demonstrated by MD simulations of these molecules bound to the active site of the main protease of the coronavirus SARS-CoV-2, 3CL
    Language English
    Publishing date 2021-03-15
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 2786545-9
    ISSN 2352-3409 ; 2352-3409
    ISSN (online) 2352-3409
    ISSN 2352-3409
    DOI 10.1016/j.dib.2021.106948
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  5. Article ; Online: Rational Drug Design of Peptide-Based Therapies for Sickle Cell Disease.

    Olubiyi, Olujide O / Olagunju, Maryam O / Strodel, Birgit

    Molecules (Basel, Switzerland)

    2019  Volume 24, Issue 24

    Abstract: Sickle cell disease (SCD) is a group of inherited disorders affecting red blood cells, which is caused by a single mutation that results in substitution of the amino acid valine for glutamic acid in the sixth position of the β-globin chain of hemoglobin. ...

    Abstract Sickle cell disease (SCD) is a group of inherited disorders affecting red blood cells, which is caused by a single mutation that results in substitution of the amino acid valine for glutamic acid in the sixth position of the β-globin chain of hemoglobin. These mutant hemoglobin molecules, called hemoglobin S, can polymerize upon deoxygenation, causing erythrocytes to adopt a sickled form and to suffer hemolysis and vaso-occlusion. Until recently, only two drug therapies for SCD, which do not even fully address the manifestations of SCD, were approved by the United States (US) Food and Drug Administration. A third treatment was newly approved, while a monoclonal antibody preventing vaso-occlusive crises is also now available. The complex nature of SCD manifestations provides multiple critical points where drug discovery efforts can be and have been directed. These notwithstanding, the need for new therapeutic approaches remains high and one of the recent efforts includes developments aimed at inhibiting the polymerization of hemoglobin S. This review focuses on anti-sickling approaches using peptide-based inhibitors, ranging from individual amino acid dipeptides investigated 30-40 years ago up to more promising 12- and 15-mers under consideration in recent years.
    MeSH term(s) Anemia, Sickle Cell/drug therapy ; Anemia, Sickle Cell/metabolism ; Anemia, Sickle Cell/pathology ; Antisickling Agents/chemistry ; Antisickling Agents/therapeutic use ; Drug Design ; Hemoglobin, Sickle/metabolism ; Humans ; Peptides/chemistry ; Peptides/therapeutic use
    Chemical Substances Antisickling Agents ; Hemoglobin, Sickle ; Peptides
    Language English
    Publishing date 2019-12-12
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 1413402-0
    ISSN 1420-3049 ; 1431-5165 ; 1420-3049
    ISSN (online) 1420-3049
    ISSN 1431-5165 ; 1420-3049
    DOI 10.3390/molecules24244551
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  6. Article: Topology and parameter data of thirteen non-natural amino acids for molecular simulations with CHARMM22.

    Olubiyi, Olujide O / Strodel, Birgit

    Data in brief

    2016  Volume 9, Page(s) 642–647

    Abstract: In this article we provide a data package containing the topology files and parameters compatible with the CHARMM22 force field for thirteen non-natural amino acids. The force field parameters were derived based on quantum mechanical (QM) calculations ... ...

    Abstract In this article we provide a data package containing the topology files and parameters compatible with the CHARMM22 force field for thirteen non-natural amino acids. The force field parameters were derived based on quantum mechanical (QM) calculations involving geometry optimization and potential energy surface scanning at the HF 6-31G(
    Language English
    Publishing date 2016-10-06
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 2786545-9
    ISSN 2352-3409
    ISSN 2352-3409
    DOI 10.1016/j.dib.2016.09.051
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  7. Article ; Online: Structural Basis of Antisickling Effects of Selected FDA Approved Drugs: A Drug Repurposing Study.

    Olubiyi, Olujide O / Olagunju, Maryam O / Oni, James O / Olubiyi, Abidemi O

    Current computer-aided drug design

    2018  Volume 14, Issue 2, Page(s) 106–116

    Abstract: Introduction: Sickle cell disease is characterized by a point mutation involving substitution of glutamic acid at position 6 to valine. Encoded in this hydrophobic mutation is both an intrinsic capacity for the beta globin molecules to assemble into ... ...

    Abstract Introduction: Sickle cell disease is characterized by a point mutation involving substitution of glutamic acid at position 6 to valine. Encoded in this hydrophobic mutation is both an intrinsic capacity for the beta globin molecules to assemble into thermodynamically favoured polymeric states as well as a rational way of interrupting the aggregation.
    Methods: In this work, starting with a theoretical model that employs occlusive binding onto the beta globin aggregation surface and using a range of computational methods and an effective energy for screening, a number of FDA approved drugs with computed aggregation inhibitory activities were identified.
    Results and conclusion: The validity of the model was confirmed using sickling tests, after which pharmacophore models as well the structural basis for the observed antisickling effects were identified.
    MeSH term(s) Anemia, Sickle Cell/drug therapy ; Anemia, Sickle Cell/genetics ; Anemia, Sickle Cell/metabolism ; Antisickling Agents/chemistry ; Antisickling Agents/pharmacology ; Drug Approval ; Drug Repositioning/methods ; Humans ; Molecular Docking Simulation ; Molecular Dynamics Simulation ; Point Mutation ; Protein Aggregates/drug effects ; United States ; United States Food and Drug Administration ; beta-Globins/genetics ; beta-Globins/metabolism
    Chemical Substances Antisickling Agents ; Protein Aggregates ; beta-Globins
    Language English
    Publishing date 2018-01-29
    Publishing country United Arab Emirates
    Document type Journal Article
    ISSN 1875-6697
    ISSN (online) 1875-6697
    DOI 10.2174/1573409914666180129163711
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  8. Article ; Online: Dataset of AMBER force field parameters of drugs, natural products and steroids for simulations using GROMACS

    Jennifer Loschwitz / Anna Jäckering / Monika Keutmann / Maryam Olagunju / Olujide O. Olubiyi / Birgit Strodel

    Data in Brief, Vol 35, Iss , Pp 106948- (2021)

    2021  

    Abstract: We provide general AMBER force field (GAFF) parameters for 160 organic molecules including drugs, natural products, and steroids, which can be employed without further processing in molecular dynamics (MD) simulations using GROMACS. We determined these ... ...

    Abstract We provide general AMBER force field (GAFF) parameters for 160 organic molecules including drugs, natural products, and steroids, which can be employed without further processing in molecular dynamics (MD) simulations using GROMACS. We determined these parameters based on quantum mechanical (QM) calculations involving geometry optimization at the HF6-31G* level of theory. For each molecule we provide a coordinate file of the three-dimensional molecular structure, the topology and the parameter file. The applicability of these parameters was demonstrated by MD simulations of these molecules bound to the active site of the main protease of the coronavirus SARS-CoV-2, 3CLpro, which is a main player during viral replication causing COVID-19.
    Keywords force field parameterization ; AMBER force field ; MD simulations ; GROMACS ; Quantum mechanics ; drugs ; Computer applications to medicine. Medical informatics ; R858-859.7 ; Science (General) ; Q1-390
    Subject code 612
    Language English
    Publishing date 2021-04-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    More links

    Kategorien

  9. Book ; Online ; Thesis: Investigation of the interaction between Alzheimer's abeta peptide and aggregation inhibitors using molecular simulations

    Olubiyi, Olujide O

    2013  

    Author's details vorgelegt von Olujide O. Olubiyi
    Language English
    Size Online-Ressource
    Document type Book ; Online ; Thesis
    Thesis / German Habilitation thesis Techn. Hochsch., Diss.--Aachen, 2013
    Database Former special subject collection: coastal and deep sea fishing

    More links

    Kategorien

  10. Article: Quinoline Antimalarials Increase the Antibacterial Activity of Ampicillin.

    Olateju, Olajumoke A / Babalola, Chinedum P / Olubiyi, Olujide O / Kotila, Olayinka A / Kwasi, David A / Oaikhena, Anderson O / Okeke, Iruka N

    Frontiers in microbiology

    2021  Volume 12, Page(s) 556550

    Abstract: Bacterial and malaria co-infections are common in malaria endemic countries and thus necessitate co-administration of antibiotics and antimalarials. There have long been anecdotal clinical reports of interactions between penicillins and antimalarial ... ...

    Abstract Bacterial and malaria co-infections are common in malaria endemic countries and thus necessitate co-administration of antibiotics and antimalarials. There have long been anecdotal clinical reports of interactions between penicillins and antimalarial agents, but the nature and mechanisms of these interactions remain to be investigated. In this study, we employed antimicrobial interaction testing methods to study the effect of two antimalarials on the antibacterial activity of ampicillin
    Language English
    Publishing date 2021-06-02
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2587354-4
    ISSN 1664-302X
    ISSN 1664-302X
    DOI 10.3389/fmicb.2021.556550
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

To top