Conformational Ensembles from Experimental Data and Computer Simulations

Conformational Ensembles from Experimental Data

and Computer Simulations

Poster Abstracts

101

66-POS

Board 26

Large-scale DFT Calculation of Double-Stacked Beta Sheet Conformations

Mogus Mochena

, Stacyann Nelson

, Anant Paravastu

Florida A&M University, Tallahassee, FL, USA,

Georgia Institute of Technology, Atlanta, FL,

USA.

Understanding biological self-assembly pathways and controlling them is a challenging problem,

but is of great importance both from fundamental point view of deciphering complex biological

processes on one hand and technological applications on the other. Here we have studied

quantum mechanically how beta strands self-assemble into beta sheets to gain understanding of

the self-assembly mechanism in simple designer peptide nanofiber RADA16-I formed from

double -stacked beta sheets. According to Sawaya et al [1], there are eight distinct structures that

result from association of beta strands as they form stacked beta sheets. RADA16-I was designed

to form when the beta sheets associate in ant-parallel conformations. [2] However, recent

detailed NMR studies show that the strands combine in parallel conformations with a registry

shift of 2 residues. [3] Classical molecular dynamics calculations were performed to determine

the stable structure among the different conformations. Unfortunately, the molecular dynamics

simulations predict that most of the structural possibilities are stable, and only experiments could

identify what structures are formed in solution. We have performed linearly scaled density

functional theory (DFT) calculations on symmetric structures as suggested by Sawaya et al to

determine stable conformations.

[1] Sawaya, M. R.; Sambashivan, S.; Nelson, R.; Ivanova, M. I.; Sievers, S. A.; Apostol, M. I.;

Thompson, M. J.; Balbirnie, M.; Wiltzius, J. J. W.; McFarlane, H. T.; Madsen, A. O.; Riekel, C.;

Eisenberg, D. Nature 447, 453-457 (2007).

[2] Yokoi H, Kinoshita T, & Zhang S G, P Natl Acad Sci USA 102(24):8414-8419 (2005).

[3] Cormier, A R, Pang, X, Zimmerman, M I, Zhou, H, Paravastu A K, ACS Nano 9, 7562-7572

(2013)