A Tree-Decomposition Approach to Protein Structure Prediction
CSB '05 Proceedings of the 2005 IEEE Computational Systems Bioinformatics Conference
Fast and accurate algorithms for protein side-chain packing
Journal of the ACM (JACM)
Linear Programming Relaxations and Belief Propagation -- An Empirical Study
The Journal of Machine Learning Research
A Linear Programming Approach to Max-Sum Problem: A Review
IEEE Transactions on Pattern Analysis and Machine Intelligence
Improving Strand Pairing Prediction through Exploring Folding Cooperativity
IEEE/ACM Transactions on Computational Biology and Bioinformatics (TCBB)
An improved hybrid global optimization method for protein tertiary structure prediction
Computational Optimization and Applications
Minimizing and learning energy functions for side-chain prediction
RECOMB'07 Proceedings of the 11th annual international conference on Research in computational molecular biology
Rapid and accurate protein side chain prediction with local backbone information
RECOMB'08 Proceedings of the 12th annual international conference on Research in computational molecular biology
Design of protein-protein interactions with a novel ensemble-based scoring algorithm
RECOMB'11 Proceedings of the 15th Annual international conference on Research in computational molecular biology
RECOMB'11 Proceedings of the 15th Annual international conference on Research in computational molecular biology
A cost-aggregating integer linear program for motif finding
Journal of Discrete Algorithms
Residues with Similar Hexagon Neighborhoods Share Similar Side-Chain Conformations
IEEE/ACM Transactions on Computational Biology and Bioinformatics (TCBB)
Protein side-chain placement through MAP estimation and problem-size reduction
WABI'06 Proceedings of the 6th international conference on Algorithms in Bioinformatics
A compact mathematical programming formulation for DNA motif finding
CPM'06 Proceedings of the 17th Annual conference on Combinatorial Pattern Matching
Rapid protein side-chain packing via tree decomposition
RECOMB'05 Proceedings of the 9th Annual international conference on Research in Computational Molecular Biology
Structure-Guided deimmunization of therapeutic proteins
RECOMB'12 Proceedings of the 16th Annual international conference on Research in Computational Molecular Biology
Bringing folding pathways into strand pairing prediction
WABI'07 Proceedings of the 7th international conference on Algorithms in Bioinformatics
Computational protein design as a cost function network optimization problem
CP'12 Proceedings of the 18th international conference on Principles and Practice of Constraint Programming
Protein structure optimization by side-chain positioning via beta-complex
Journal of Global Optimization
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Motivation: Side-chain positioning is a central component of homology modeling and protein design. In a common formulation of the problem, the backbone is fixed, side-chain conformations come from a rotamer library, and a pairwise energy function is optimized. It is NP-complete to find even a reasonable approximate solution to this problem. We seek to put this hardness result into practical context. Results: We present an integer linear programming (ILP) formulation of side-chain positioning that allows us to tackle large problem sizes. We relax the integrality constraint to give a polynomial-time linear programming (LP) heuristic. We apply LP to position side chains on native and homologous backbones and to choose side chains for protein design. Surprisingly, when positioning side chains on native and homologous backbones, optimal solutions using a simple, biologically relevant energy function can usually be found using LP. On the other hand, the design problem often cannot be solved using LP directly; however, optimal solutions for large instances can still be found using the computationally more expensive ILP procedure. While different energy functions also affect the difficulty of the problem, the LP/ILP approach is able to find optimal solutions. Our analysis is the first large-scale demonstration that LP-based approaches are highly effective in finding optimal (and successive near-optimal) solutions for the side-chain positioning problem. Availability: The source code for generating the ILP given a file of pairwise energies between rotamers is available online at http://compbio.cs.princeton.edu/scplp Contact: msingh@cs.princeton.edu