Download Phase behaviour and transitions of peptides and proteins

Phase behaviour and transitions of peptides and proteins
Raffaela Cabriolu and Stefan Auer
Introduction
My research is focused on the application of theoretical computational tools developed in soft
condensed matter physics to investigate the phase behaviour and transitions of complex
systems of biomolecules. From a purely statistical mechanical point of view an ensemble of
many peptides and proteins represents a new and important system which should lead to
bridge our understanding of colloidal systems, polymers, and proteins. The research
highlights in the year 2010 were the calculation of a phase diagram of natively folded αhelical and unfolded β-sheet forming peptides and the application of nucleation theory to
amyloid fibril formation.
Phase diagram of α-helical and β-sheet forming peptides.
The intrinsic property of proteins to form structural motifs such as α helices and β sheets
leads to a complex phase behavior in which proteins can assemble into various types of
aggregates including crystals, liquidlike phases of unfolded or natively folded proteins, and
amyloid fibrils. In this work we use a coarse-grained protein model that enables us to perform
Monte Carlo simulations for determining the phase diagram of natively folded α-helical and
unfolded β-sheet forming peptides. The simulations reveal the existence of various metastable
peptide phases. The liquidlike phases are metastable with respect to the fibrillar phases, and
there is a hierarchy of metastability.
The application of nucleation theory to amyloid fibril formation.
The assembly of proteins into amyloid fibrils is a widespread and much-studied phenomenon,
because it has wide implications ranging from biotechnology to human disease. Yet, the
nucleation of such nanofibrils is poorly understood. In our work we try to illustrate that
amyloid formation might follow a common fibril nucleation mechanism which could be
treated in the framework of existing general theories of nucleation of new phases. Progress to
support this view was made in our recent work, where we used concepts from the theory of
overall crystallization to describe the kinetics of overall protein aggregation, and applied
classical and atomistic nucleation theories to describe the nucleation of amyloid fibrils.
Publications
Auer, S. & Kashchiev, D. (2010) Phase diagram of α-helical and β-sheet forming peptides.
Phys. Rev. Lett. 104:168105.
Auer, S. & Kashchiev, D. (2010) Insight into the correlation between lag time and
aggregation in the kinetics of protein aggregation. Proteins 78:2412.
Cabriolu, R., Kashchiev, D. & Auer, S. (2010) Atomistic nucleation theory of amyloid fibrils
formation. J. Chem. Phys. 133:225101.
Kashchiev, D. & Auer, S. (2010) Nucleation of amyloid fibrils. J. Chem. Phys. 132:215101.
Funding
This work was supported by the EPSRC-GB Grant No. EP/G026165/1.
Collaborators
Dimo Kashchiev (Sofia).