Conformational Ensembles from Experimental Data and Computer Simulations

Conformational Ensembles from Experimental Data and Computer Simulations

Poster Abstracts

66-POS Board 26 Large-scale DFT Calculation of Double-Stacked Beta Sheet Conformations Mogus Mochena 1 , Stacyann Nelson 1 , Anant Paravastu 2 . 1 Florida A&M University, Tallahassee, FL, USA, 2 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)

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