The influences of E22Q mutant on solvated 3Aβ 11-40 peptide: A REMD study
| Autor: | Huynh Minh Hung, Nguyen Thanh Tung, Nam Dao Hong, Son Tung Ngo |
|---|---|
| Přispěvatelé: | Pharmaceutical and Pharmacological Sciences, Department of Analytical Chemistry, Applied Chemometrics and Molecular Modelling |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
chemistry.chemical_classification biology Amyloid beta Mutant Peptide Trimer biology.organism_classification Computer Graphics and Computer-Aided Design 03 medical and health sciences Crystallography Molecular dynamics 030104 developmental biology 0302 clinical medicine chemistry Sasa Materials Chemistry biology.protein Salt bridge Physical and Theoretical Chemistry Protein secondary structure 030217 neurology & neurosurgery Spectroscopy |
| Zdroj: | Journal of Molecular Graphics and Modelling. 83:122-128 |
| ISSN: | 1093-3263 |
| Popis: | The residue E22 plays a critical role in the aggregation process of Amyloid beta (Aβ) peptides. The effect of E22Q mutant on the shapes of the solvated Aβ11-40 trimer is clarified using a replica exchange molecular dynamics (REMD) simulation employing ∼20.6 μs of MD simulations with 48 disparate replicas. The increase of intramolecular polar contacts and salt bridge between the residue D23 to residues (24–29) was observed. The residual secondary structure of the mutated trimer is shifted in a similar way to the picture observed in previous investigations of F19W mutant. The free energy surface (FES) of the mutated E22Q system has a fewer number of minima in comparison with the wild-type trimer. The optimized shapes of the mutated E22Q form a significant increase in beta structure (47%) and serious decrease in coil content (46%) compared with the wild-type (of 36 and 56%, respectively). The binding affinity of constituting chains to the rest is of −43.7 ± 6.5 kcal/mol, implying that the representative structure of E22Q is more stable than the wild-type one. Furthermore, the E22Q mutant increases the size of stable structures due to larger collision cross section (CCS) and solvent accessible area (SASA). The observed results may enhance the Aβ inhibition throughout the contribution to the knowledge of the Aβ oligomerization/aggregation. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect