Modeling of Biomolecular Systems Interactions, Dynamics, and Allostery: Bridging Experiments and Computations - September 10-14, 2014, Istanbul, Turkey

Modeling of Biomolecular Systems Interactions, Dynamics, and Allostery Poster Session I

6-POS Board 6 Translocation across the Membrane Analyzed by Dimensionality Reduction Begüm Alaybeyoglu , Elif Ozkirimli Olmez. Bogazici University, Istanbul, Turkey.

Peptide drugs are promising drug leads due to their high specificity and affinity to targets, but their use as therapeutics against intracellular targets is limited because of difficulty in delivery into the cell. In the general context of drug delivery, cell-penetrating peptides (CPPs) were discovered based on translocating ability of some proteins. Computational studies such as molecular dynamics (MD) simulations of peptide – membrane systems have focused on the behavior and effects of the peptide inside the membrane or to examine whether a spontaneous adsorption and insertion into the membrane would occur. On the other hand, steered molecular dynamics (SMD) simulations, have been favored to obtain time dependent atomic level information on long time scale events such as drug binding, water transport across aquaporin and unfolding. The computational simulation of membrane translocation is a complex process and gives a huge number of conformations in the form of Cartesian coordinates for each of the atoms. In order to quantitatively characterize a computer simulation and extract the important information of the motion, a low-dimensional embedding such that the properties of the underlying manifold is preserved should be defined. Finding a set of coordinates in which very few of them show significant variation and the others may considered almost constant is mathematically called dimensionality reduction problem. In an effort to characterize the translocation of the 18-residue long cell-penetrating peptide pVEC (LLIILRRRIRKQAHAHSK) and its variants through a lipid bilayer, we performed steered molecular dynamic (SMD) simulations, in which force is applied on the peptide to move it from one side of the membrane to the other. Here, we present an approach for the theoretical characterization of the nonlinear process of membrane uptake based on the idea of dimensionality reduction.

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