Docking and Molecular Dynamics Simulations Clarify Binding Sites for Interactions of Novel Marine Sulfated Glycans with SARS-CoV-2 Spike Glycoprotein.
Priyanka SamantaSushil K MishraVitor H PominRobert J DoerksenPublished in: Molecules (Basel, Switzerland) (2023)
The entry of SARS-CoV-2 into the host cell is mediated by its S-glycoprotein (SGP). Sulfated glycans bind to the SGP receptor-binding domain (RBD), which forms a ternary complex with its receptor angiotensin converting enzyme 2. Here, we have conducted a thorough and systematic computational study of the binding of four oligosaccharide building blocks from novel marine sulfated glycans (isolated from Pentacta pygmaea and Isostichopus badionotus ) to the non-glycosylated and glycosylated RBD. Blind docking studies using three docking programs identified five potential cryptic binding sites. Extensive site-targeted docking and molecular dynamics simulations using two force fields confirmed only two binding sites (Sites 1 and 5) for these novel, highly charged sulfated glycans, which were also confirmed by previously published reports. This work showed the structural features and key interactions driving ligand binding. A previous study predicted Site 2 to be a potential binding site, which was not observed here. The use of several molecular modeling approaches gave a comprehensive assessment. The detailed comparative study utilizing multiple modeling approaches is the first of its kind for novel glycan-SGP interaction characterization. This study provided insights into the key structural features of these novel glycans as they are considered for development as potential therapeutics.
Keyphrases
- molecular dynamics simulations
- sars cov
- cell surface
- molecular docking
- angiotensin converting enzyme
- molecular dynamics
- binding protein
- angiotensin ii
- small molecule
- public health
- randomized controlled trial
- protein protein
- stem cells
- single cell
- cell therapy
- dna binding
- transcription factor
- drug delivery
- risk assessment
- cancer therapy
- coronavirus disease