title: How good are simplified models for protein structure prediction?
abstract: Protein structure prediction (PSP) has been one of the most challenging problems in computational biology for several decades. The challenge is largely due to the complexity of the all-atomic details and the unknown nature of the energy function. Researchers have therefore used simplified energy models that consider interaction potentials only between the amino acid monomers in contact on discrete lattices. The restricted nature of the lattices and the energy models poses a twofold concern regarding the assessment of the models. Can a native or a very close structure be obtained when structures are mapped to lattices? Can the contact based energy models on discrete lattices guide the search towards the native structures? In this paper, we use the protein chain lattice fitting (PCLF) problem to address the first concern; we developed a constraint-based local search algorithm for the PCLF problem for cubic and face-centered cubic lattices and found very close lattice fits for the native structures. For the second concern, we use a number of techniques to sample the conformation space and find correlations between energy functions and root mean square deviation (RMSD) distance of the lattice-based structures with the native structures. Our analysis reveals weakness of several contact based energy models used that are popular in PSP.
authors.affiliation: Institute for Integrated and Intelligent Systems (IIIS), Griffith University, 170 Kessels Road, Nathan, QLD 4111, Australia ; Queensland Research Laboratory, National ICT of Australia (NICTA), GPO Box 2434, Brisbane, QLD 4001, Australia.
authors.forename: Swakkhar
authors.identifier: 0000-0003-4954-524X
authors.initials: S
authors.lastname: Shatabda
authors.affiliation: Institute for Integrated and Intelligent Systems (IIIS), Griffith University, 170 Kessels Road, Nathan, QLD 4111, Australia.
authors.forename: M A Hakim
authors.initials: MA
authors.lastname: Newton
authors.affiliation: Institute for Integrated and Intelligent Systems (IIIS), Griffith University, 170 Kessels Road, Nathan, QLD 4111, Australia ; Queensland Research Laboratory, National ICT of Australia (NICTA), GPO Box 2434, Brisbane, QLD 4001, Australia.
authors.forename: Mahmood A
authors.initials: MA
authors.lastname: Rashid
authors.affiliation: Institute for Integrated and Intelligent Systems (IIIS), Griffith University, 170 Kessels Road, Nathan, QLD 4111, Australia.
authors.forename: Duc Nghia
authors.initials: DN
authors.lastname: Pham
authors.affiliation: Institute for Integrated and Intelligent Systems (IIIS), Griffith University, 170 Kessels Road, Nathan, QLD 4111, Australia ; Queensland Research Laboratory, National ICT of Australia (NICTA), GPO Box 2434, Brisbane, QLD 4001, Australia.
authors.forename: Abdul
authors.initials: A
authors.lastname: Sattar