Conformational Ensembles from Experimental Data and Computer Simulations

Conformational Ensembles from Experimental Data and Computer Simulations

Poster Abstracts

78-POS Board 38 Using the cgDNA Coarse-grain Model to Generate Sequence-dependent DNA Configuration Ensembles Daiva Petkeviciute 1,2 . 1 Ecole Polytechniqye Fédérale de Lausanne, Lausanne, Switzerland, 2 Kaunas University of Technology, Kaunas, Lithuania. The cgDNA coarse-grain model and its associated cgDNAmc Monte Carlo code [1, 2, 3] can generate large equilibrium ensembles of configurations of naked B-DNA fragments in solution. The appropriate length of such a fragment can vary from 10 to 10^4 base pairs, with any DNA sequence being specified. For sequence length of 300 base pairs 1 million configurations can be generated in approximately three minutes on a single processor [3]. The resulting ensembles are strongly dependent on the sequence, e.g. as manifested in both the average shape and flexibility. The model parameter sets are trained on libraries of Molecular Dynamics simulations, that are many orders of magnitude more computationally demanding then the cgDNAmc code. At the length scale of tens of bases model predictions can be compared with X-ray crystal structure and NMR data, and the fits are shown to be in rather good agreement [2]. Another target application of the model is estimating looping and cyclisation j factors [4]. Here we use the cgDNAmc to study various notions of DNA persistence length [3]. [1] A sequence-dependent rigid-base model of DNA. O. Gonzalez, D. Petkevičiūtė, J. H. Maddocks, J. Chem. Phys. 138 (5), 2013. [2] cgDNA: a software package for the prediction of sequence-dependent coarse-grain free energies of B-form DNA. D. Petkevičiūtė, M. Pasi, O. Gonzalez and J. H. Maddocks, Nucleic Acids Res. 42 (20), 2014. [3] Sequence-dependent persistence lengths of DNA. J. S. Mitchell, J. Glowacki, A. E. Grandchamp, R. S. Manning and J. H. Maddocks, J. Chem. Theory Comput., 2016. DOI: 10.1021/acs.jctc.6b00904. [4] DNA flexibility studied by covalent closure of short fragments into circles. D. Shore, J. Langowski, R. L. Baldwin, Proc. Natl. Acad. Sci. USA 1981, 78, 4833–4837.

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