Program

I.15 -- Invited, IWTCP-3

Date: Wednesday, 29 July 2015

Time: 16h00 - 16h35

Protein aggregation: Key principles and applications

Mai Suan Li (1,2)

(1) Institute of Physics, Polish Academy of Sciences, Al. Lotnikow 32/46, Warsaw, Poland; (2) Institute for Computational Science and Technology at Ho Chi Minh City, Quang Trung Software City, Tan Chanh Hiep Ward, District 12, HCM city, Vietnam

Protein aggregation is presumably associated with a large group of major human diseases including Alzheimer’s disease (AD), prion disorders, type 2 diabetes etc. Therefore, understanding the key factors that control this process is important not only for basic research but also for drug design for relevant diseases . The fibrillogenesis of polypeptide chains depends on their intrinsic properties as well as on external conditions. Using coarse grained and all-atom models we show that fibril formation times are strongly correlated with hydrophobicity, charges and population of the so called fibril-prone conformation N* in monomer state. The higher is the N* population the faster is the fibril elongation and this dependence may be described by a single exponential function. Our results open up a new way to understand the propensity of biomolecules to aggregation at monomer level.

We will discuss the ways of blocking aggregation and destroying fibers of amyloid beta peptides the self-assembly of which is believed to be the main cause of AD. Through in silico and in vitro experiments small molecules from large data bases and short peptides have been obtained as potential candidates for treating AD due to their strong binding to amyloid beta aggregates. Picosecond dissociation of amyloid fibrils with infrared laser will be discussed. Nonequilibrium simulation studies show that the fibril is destroyed due to the strong resonance between its amide I vibrational modes and the laser field, not just the deposited infrared thermal energy.

1. J. Nasica-Labouze et al, Chem Rev 115, 3518-3563 (2015)
2. M.S. Li, N.T Co, , G. Reddy, C-K Hu and D. Thirumalai, Phys. Rev. Lett. 105, 218101 (2010)
3. P. M. Truong, M.H. Viet, P.H. Nguyen, C. K. Hu, and M.S. Li, J. Phys. Chem. B 118, 8972 (2014)
4. P.D.Q. Huy and M.S. Li, Phys Chem Chem Phys 16, 20030-20040 (2014)
5. M.H. Viet, S.T. Ngo, N.S. Lam , and M.S. Li, J. Phys. Chem. B 115, 7433 (2011)

Presenter: Mai Suan Li