Combinatorial Virtual Library Screening Study of Transforming Growth Factor-β2-Chondroitin Sulfate System.


Journal

International journal of molecular sciences
ISSN: 1422-0067
Titre abrégé: Int J Mol Sci
Pays: Switzerland
ID NLM: 101092791

Informations de publication

Date de publication:
14 Jul 2021
Historique:
received: 08 06 2021
revised: 10 07 2021
accepted: 12 07 2021
entrez: 24 7 2021
pubmed: 25 7 2021
medline: 31 7 2021
Statut: epublish

Résumé

Transforming growth factor-beta (TGF-β), a member of the TGF-β cytokine superfamily, is known to bind to sulfated glycosaminoglycans (GAGs), but the nature of this interaction remains unclear. In a recent study, we found that preterm human milk TGF-β2 is sequestered by chondroitin sulfate (CS) in its proteoglycan form. To understand the molecular basis of the TGF-β2-CS interaction, we utilized the computational combinatorial virtual library screening (CVLS) approach in tandem with molecular dynamics (MD) simulations. All possible CS oligosaccharides were generated in a combinatorial manner to give 24 di- (CS02), 192 tetra- (CS04), and 1536 hexa- (CS06) saccharides. This library of 1752 CS oligosaccharides was first screened against TGF-β2 using the dual filter CVLS algorithm in which the GOLDScore and root-mean-square-difference (RMSD) between the best bound poses were used as surrogate markers for in silico

Identifiants

pubmed: 34299163
pii: ijms22147542
doi: 10.3390/ijms22147542
pmc: PMC8305211
pii:
doi:

Substances chimiques

Transforming Growth Factor beta2 0
Chondroitin Sulfates 9007-28-7

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Subventions

Organisme : NIH HHS
ID : HL107152
Pays : United States
Organisme : NIH HHS
ID : HL151333
Pays : United States
Organisme : NIH HHS
ID : CA241951
Pays : United States

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Auteurs

Nehru Viji Sankaranarayanan (NV)

Institute for Structural Biology, Drug Discovery and Development, Virginia Commonwealth University, Richmond, VA 23219, USA.
Department of Medicinal Chemistry, Virginia Commonwealth University, Richmond, VA 23298, USA.

Balaji Nagarajan (B)

Institute for Structural Biology, Drug Discovery and Development, Virginia Commonwealth University, Richmond, VA 23219, USA.
Department of Medicinal Chemistry, Virginia Commonwealth University, Richmond, VA 23298, USA.

Umesh R Desai (UR)

Institute for Structural Biology, Drug Discovery and Development, Virginia Commonwealth University, Richmond, VA 23219, USA.
Department of Medicinal Chemistry, Virginia Commonwealth University, Richmond, VA 23298, USA.

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