Computational insights into dynamics of protein aggregation and enzyme-substrate interactions

Mehmet Ozbil, Arghya Barman, Ram Prasad Bora, Rajeev Prabhakar

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

In this Perspective, the roles of protein dynamics have been discussed in the aggregation of amyloid beta (Aβ) peptides and formation of enzyme-substrate complexes of beta-secretase (BACE1) and insulin-degrading enzyme (IDE). The studies regarding the influence of individual amino acid residues and specific regions on the structures and oligomerization of early Aβ aggregates and computations of their translational and rotational diffusion coefficients and order parameters exhibited that even the short-time-scale molecular dynamics simulations can reproduce certain experimental parameters with reasonable accuracy. The simulations elucidating the enzyme-substrate interactions of BACE1 and IDE successfully showed that the chemical nature and length of the substrates influence the dynamics and plasticity of both the enzyme and substrate. An atomic-level understanding of these processes will advance our efforts to develop therapeutic strategies for several deadly diseases through the design of small molecules with antiaggregation properties and substrate-specific designer forms of enzymes.

Original languageEnglish
Pages (from-to)3460-3469
Number of pages10
JournalJournal of Physical Chemistry Letters
Volume3
Issue number23
DOIs
StatePublished - Dec 6 2012

Fingerprint

enzymes
Agglomeration
Enzymes
proteins
Proteins
Insulysin
Substrates
insulin
Insulin
interactions
Amyloid Precursor Protein Secretases
Oligomerization
Amyloid
Plasticity
Molecular dynamics
plastic properties
Peptides
peptides
amino acids
Amino acids

ASJC Scopus subject areas

  • Materials Science(all)

Cite this

Computational insights into dynamics of protein aggregation and enzyme-substrate interactions. / Ozbil, Mehmet; Barman, Arghya; Bora, Ram Prasad; Prabhakar, Rajeev.

In: Journal of Physical Chemistry Letters, Vol. 3, No. 23, 06.12.2012, p. 3460-3469.

Research output: Contribution to journalArticle

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