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Structure Prediction of Loops with Fixed and Flexible Stems

Author(s): Subramani, A; Floudas, CA

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Abstract: The prediction of loop structures is considered one of the main challenges in the protein folding problem. Regardless of the dependence of the overall algorithm on the protein data bank, the flexibility of loop regions dictates the need for special attention to their structures. In this article, we present algorithms for loop structure prediction with fixed stem and flexible stem geometry. In the flexible stem geometry problem, only the secondary structure of three stem residues on either side of the loop is known. In the fixed stem geometry problem, the structure of the three stem residues on either side of the loop is also known. Initial loop structures are generated using a probability database for the flexible stem geometry problem, and using torsion angle dynamics for the fixed stem geometry problem. Three rotamer optimization algorithms are introduced to alleviate steric clashes between the generated backbone structures and the side chain rotamers. The structures are optimized by energy minimization using an all-atom force field. The optimized structures are clustered using a traveling salesman problem-based clustering algorithm. The structures in the densest clusters are then utilized to refine dihedral angle bounds on all amino acids in the loop. The entire procedure is carried out for a number of iterations, leading to improved structure prediction and refined dihedral angle bounds. The algorithms presented in this article have been tested on 3190 loops from the PDBSelect25 data set and on targets from the recently concluded CASP9 community-wide experiment.
Publication Date: 18-Feb-2012
Citation: Subramani, A., and Christodoulos. A. Floudas. "Structure Prediction of Loops with Fixed and Flexible Stems." The Journal of Physical Chemistry B 116, no. 23 (2012): 6670-6682. doi: 10.1021/jp2113957
DOI: doi:10.1021/jp2113957
ISSN: 1520-6106
EISSN: 1520-5207
Pages: 6670 - 6682
Type of Material: Journal Article
Journal/Proceeding Title: The Journal of Physical Chemistry B
Version: Author's manuscript

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