Significance of Knotted Structures for Function of Proteins and Nucleic Acids - September 17-21, 2014

Significance of Knotted Structures for Function of Proteins and Nucleic Acids

Poster Session I

9 – POS Board 9 Sequence-dependent Potentials of Mean Force and Fragmentary Experimental Data in Modeling the Spatial Structure of Proteins Aleksandra Dawid , Dominik Gront and Andrzej Kolinski Faculty of Chemistry, University of Warsaw, Poland Since the first complete crystallization of the protein structure have passed more than half a century. During this time, both experimentalists and theorists, were focused on discovering the secrets of evolution. Their work has provided valuable knowledge, but the heart of the matter remains unexplained. This is a serious problem whose solution would be to drive the development of many areas of life. The process of proteins folding is highly complex and depends on a number of parameters. No universal factor initiating the process and controlling its proper course. A huge number of physico- chemical interactions of short and long-range determines the precise position of atoms in space. Taking into account the numerous technical difficulties, cost and effort associated with the experimental assignment of the structure of proteins and the large scale of the problem, it is necessary to improve automated methods of theoretical modeling. The growing content of the PDB database encouraged us to once again analyze these spatial distributions. Our analysis, conducted for planar and torsional angles as well as for local distances between the residues may be valuable for deriving the potentials of mean force, which are useful in the prediction of secondary structure and protein folding simulations. Each of them is a potential of mean force (PMF) based on knowledge, because it was obtained as a result of the statistical analysis of the local geometry of the main chain of proteins of known structure. PMF is based on an approximated probability distribution function along a coordinate, which is derived from a Boltzmann weighted average. It is useful to know how the free energy changes as a function of reaction coordinates, such as the distance between two atoms or the torsion angle of a bond in a molecule. There are two groups of new potentials in the form of the kernel density estimation (KDE), intended for simulating models with varying degrees of complexity. For the coarse-grained representation of CABS model there are three potentials: the distance - R15, plane angle - A13, torsion angle - T14. For the coarse-grained model with full backbone there is a potential of torsion angle Phi-Psi. The specificity of the obtained potentials was assessed as results of isothermal simulation using the new force field and the dynamics of the Monte Carlo. Also, the folding process of proteins, which come from benchmark, was simulated with a de novo method for Replica Exchange Monte Carlo. Our ultimate goal is to create a multiscale protocol to obtain the spatial structure of proteins, so we have both PMFs for full atom and coarse grained.

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