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

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

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

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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
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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
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Article: 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 Apr., v. 35

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	COVID-19 infection ; Severe acute respiratory syndrome coronavirus 2 ; active sites ; data collection ; geometry ; molecular dynamics ; proteinases ; quantum mechanics ; topology ; virus replication
Language	English
Dates of publication	2021-04
Publishing place	Elsevier Inc.
Document type	Article
ZDB-ID	2786545-9
ISSN	2352-3409
ISSN	2352-3409
DOI	10.1016/j.dib.2021.106948
Database	NAL-Catalogue (AGRICOLA)

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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

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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 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

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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 Dec., v. 9

2016

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(d) and HF 6-311G(d,p) levels of theory. The resulting energy data points were fitted to mathematical functions representing each component of the CHARMM22 force field. Further fine-tuning of the parameters utilized molecular mechanics energies, which were iteratively calculated and compared to the corresponding QM values until the latter were satisfactorily reproduced. The final force field data were validated with molecular dynamics simulations in explicit solvent conditions.
Keywords	geometry ; molecular dynamics ; potential energy ; quantum mechanics ; solvents ; topology
Language	English
Dates of publication	2016-12
Size	p. 642-647.
Publishing place	Elsevier Inc.
Document type	Article
ZDB-ID	2786545-9
ISSN	2352-3409
ISSN	2352-3409
DOI	10.1016/j.dib.2016.09.051
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Antibiofilm agents with therapeutic potential against enteroaggregative Escherichia coli.

Kwasi, David A / Babalola, Chinedum P / Olubiyi, Olujide O / Hoffmann, Jennifer / Uzochukwu, Ikemefuna C / Okeke, Iruka N

PLoS neglected tropical diseases

2022 Volume 16, Issue 10, Page(s) e0010809

Abstract: Background: Enteroaggregative Escherichia coli (EAEC) is a predominant but neglected enteric pathogen implicated in infantile diarrhoea and nutrient malabsorption. There are no non-antibiotic approaches to dealing with persistent infection by these ... ...

Abstract	Background: Enteroaggregative Escherichia coli (EAEC) is a predominant but neglected enteric pathogen implicated in infantile diarrhoea and nutrient malabsorption. There are no non-antibiotic approaches to dealing with persistent infection by these exceptional colonizers, which form copious biofilms. We screened the Medicines for Malaria Venture Pathogen Box for chemical entities that inhibit EAEC biofilm formation. Methodology: We used EAEC strains, 042 and MND005E in a medium-throughput crystal violet-based antibiofilm screen. Hits were confirmed in concentration-dependence, growth kinetic and time course assays and activity spectra were determined against a panel of 25 other EAEC strains. Antibiofilm activity against isogenic EAEC mutants, molecular docking simulations and comparative genomic analysis were used to identify the mechanism of action of one hit. Principal findings: In all, five compounds (1.25%) reproducibly inhibited biofilm accumulation by at least one strain by 30-85% while inhibiting growth by under 10%. Hits exhibited potent antibiofilm activity at concentrations at least 10-fold lower than those reported for nitazoxanide, the only known EAEC biofilm inhibitor. Reflective of known EAEC heterogeneity, only one hit was active against both screen isolates, but three hits showed broad antibiofilm activity against a larger panel of strains. Mechanism of action studies point to the EAEC anti-aggregation protein (Aap), dispersin, as the target of compound MMV687800. Conclusions: This study identified five compounds, not previously described as anti-adhesins or Gram-negative antibacterials, with significant EAEC antibiofilm activity. Molecule, MMV687800 targets the EAEC Aap. In vitro small-molecule inhibition of EAEC colonization opens a way to new therapeutic approaches against EAEC infection.
MeSH term(s)	Humans ; Escherichia coli/genetics ; Escherichia coli Proteins/genetics ; Escherichia coli Proteins/metabolism ; Gentian Violet ; Molecular Docking Simulation ; Escherichia coli Infections/drug therapy ; Biofilms ; Complement Inactivating Agents ; Diarrhea
Chemical Substances	Escherichia coli Proteins ; Gentian Violet (J4Z741D6O5) ; Complement Inactivating Agents
Language	English
Publishing date	2022-10-06
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2429704-5
ISSN	1935-2735 ; 1935-2735
ISSN (online)	1935-2735
ISSN	1935-2735
DOI	10.1371/journal.pntd.0010809
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Computational Prospecting for the Pharmacological Mechanism of Activity: HIV-1 Inhibition by Ixoratannin A-2.

Olubiyi, Olujide O / Idowu, Thomas O / Ogundaini, Abiodun O / Orhuah, Goodness

Current computer-aided drug design

2019 Volume 16, Issue 4, Page(s) 376–388

Abstract: Background: Ixora coccinea is a tropical ornamental shrub employed in ethnomedicine for the treatment of a number of diseases none of which include the Human Immunodeficiency Virus (HIV) infection. Ixoratannin A-2, one of the constituents, was ... ...

Abstract	Background: Ixora coccinea is a tropical ornamental shrub employed in ethnomedicine for the treatment of a number of diseases none of which include the Human Immunodeficiency Virus (HIV) infection. Ixoratannin A-2, one of the constituents, was previously identified via virtual-screening and experimentally confirmed to possess significant anti-HIV-1 activity in an in vitro CD4+ replication assay. This activity was observed to be significantly reduced in degree in viruses lacking the protein Vpu. This suggests the involvement of Vpu as well as other extra-Vpu macromolecules in its antiviral activity. Methods: In the present computational search for the identity of the other macromolecules that could possibly explain the observed activity, a panel of fourteen established HIV-1 macromolecular targets was assembled against which ixoratannin A-2 and other major phytoconstituents of I. coccinea were virtually screened. Results: Structural analyses of the computed ligand-bound complexes, as well as the careful investigation of the thermodynamic attributes of the predicted binding, revealed subtle selectivity patterns at the atomistic level that suggest the likely involvement of multiple macromolecular processes. Some of the binding interactions were found to be thermodynamically favourable, including the multidrug-resistant HIV protease enzyme, CXCR4 and the human elongin C protein all of which formed reasonably strong interactions with ixoratannin A-2 and other constituents of I. coccinea. Conclusion: Ixoratannin A-2's ability to favourably interact with multiple HIV-1 and human targets could explain its observed extra-Vpu antiviral activity. This, however, does not imply uncontrolled binding with all available targets; on the other hand, molecular size of ixoratannin A-2 and combination of functional groups confer on it a decent level of selectivity against many of the investigated HIV/AIDS targets.
MeSH term(s)	Antiviral Agents/pharmacology ; HIV Infections/drug therapy ; HIV Infections/metabolism ; HIV-1/drug effects ; HIV-1/metabolism ; Humans ; Molecular Docking Simulation ; Proanthocyanidins/pharmacology ; Protein Interaction Maps/drug effects ; Thermodynamics
Chemical Substances	Antiviral Agents ; Proanthocyanidins ; ixoratannin A-2
Language	English
Publishing date	2019-07-02
Publishing country	United Arab Emirates
Document type	Journal Article
ISSN	1875-6697
ISSN (online)	1875-6697
DOI	10.2174/1573409915666190702111023
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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

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