Dead-End Elimination with Backbone Flexibility

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چکیده

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Dead-End Elimination with Backbone Flexibility

MOTIVATION Dead-End Elimination (DEE) is a powerful algorithm capable of reducing the search space for structure-based protein design by a combinatorial factor. By using a fixed backbone template, a rotamer library, and a potential energy function, DEE identifies and prunes rotamer choices that are provably not part of the Global Minimum Energy Conformation (GMEC), effectively eliminating the m...

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Computational protein and drug design generally require accurate modeling of protein conformations. This modeling typically starts with an experimentally determined protein structure and considers possible conformational changes due to mutations or new ligands. The DEE/A* algorithm provably finds the global minimum-energy conformation (GMEC) of a protein assuming that the backbone does not move...

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A novel, yet simple and automated, protocol for reconstruction of complete peptide backbones from C(alpha) coordinates only is described, validated, and benchmarked. The described method collates a set of possible backbone conformations for each set of residue triads from a structural library derived from the PDB. The optimal permutation of these three residue segments of backbone conformations...

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Dead-End Elimination for Weighted CSP

Soft neighborhood substitutability (SNS) is a powerful technique to automatically detect and prune dominated solutions in combinatorial optimization. Recently, it has been shown in [26] that enforcing partial SNS (PSNS) during search can be worthwhile in the context of Weighted Constraint Satisfaction Problems (WCSP). However, for some problems, especially with large domains, PSNS is still too ...

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In protein redesign one of the main challenges is the ability to evaluate many different conformations of the redesigned protein in order to determine the best structure. One approach to this problem is to provably get rid of bad protein conformations using dead-end elimination (DEE). DEE was first developed for application to protein structure evaluation by Desmet et al. [1]. Since then there ...

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ژورنال

عنوان ژورنال: Bioinformatics

سال: 2007

ISSN: 1460-2059,1367-4803

DOI: 10.1093/bioinformatics/btm197