Theory of Sequence Effects in Amyloid Aggregation.
J Phys Chem B
; 122(21): 5567-5578, 2018 05 31.
Article
de En
| MEDLINE
| ID: mdl-29486561
ABSTRACT
We present a simple model for the effect of amino acid sequences on amyloid fibril formation. Using the HP model we find the binding lifetimes of four simple sequences by solving the first passage time for the intermolecular H-bond reaction coordinate. We find that sequences with identical binding energies have widely varying binding times depending on where the aggregation prone amino acids are located in the sequence. In general, longer binding times occur when the aggregation prone amino acids are clustered in a single "hot spot". Similarly, binding times are shortened by clustering weakly bound residues. Both of these effects are explained by an increase in the multiplicity of unbinding trajectories that comes from adding weak binding residues. Our model predicts a transition from ordered to disordered fibrils as the concentration of monomers increases. We apply our model to Aß, IAPP, and apomyoglobin using binding energy estimates derived from bioinformatics. We find that these sequences are highly selective of the in-register state. This selectivity arises from the having strongly bound segments of varying length and separation.
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Apoprotéines
/
Peptides bêta-amyloïdes
/
Polypeptide amyloïde des ilots
/
Myoglobine
Type d'étude:
Prognostic_studies
Langue:
En
Journal:
J Phys Chem B
Sujet du journal:
QUIMICA
Année:
2018
Type de document:
Article
Pays d'affiliation:
États-Unis d'Amérique