Book of Abstracts: Albany 2011
June 14-18 2011
©Adenine Press (2010)
Exploring Fast Protein Folding Funnel Using Replica Exchange Molecular Dynamics at Different Temperature Ranges
Protein folding is a biological process through which one dimensional sequence acquires its three dimensional structure. During past four decades various aspects of protein folding have been explored experimentally and theoretically. There have been some success in predicting 3D structure of proteins using statistical potentials (for example see references 1, 2). Reaching the experimental time scale of millisecond is a grand challenge for protein folding simulations. With the development of advanced Molecular Dynamics (MD) techniques like Replica Exchange Molecular Dynamics (REMD), simulations can possibly reach to the experimental timescales. The major difficulty in experimental studies of protein folding lies in capturing of transient intermediates and events, which is possible via performing very long simulations. Here an attempt has been made to reach the multi-microsecond simulation time scale by carrying out folding simulation on a fast folding three helix bundle protein using REMD. REMD based folding simulation has been carried out on Villin headpiece (PDB code 1VII, Fig. 1), a 36-residue small protein (3) and Engrailed Homeodomain (PDB ID: 1ENH), a 54 residue protein (4) starting from its extended structure. The multiple REMD simulations were carried out at moderate and broader temperature range. The population landscape has been built using segment wise Root Mean Square Deviation (RMSD), Principal Component Analysis (PCA) as reaction coordinates. The REMD has helped to carry out very long time scales simulations where results are close to the experimental findings. Also the effect of temperature range on the population landscape has been discussed in detail.
Figure 1: NMR structure showing the three helices along with the amino acid sequence of same (pdb code 1VII).