Inverse Protein Folding in 3D Hexagonal Prism Lattice under HPC Model

被引:3
作者
Khodabakhshi, Alireza Hadj [1 ]
Manuch, Jan [1 ]
Rafiey, Arash [1 ]
Gupta, Arvind [1 ]
机构
[1] Simon Fraser Univ, Sch Comp Sci, Burnaby, BC V5A 1S6, Canada
关键词
computational molecular biology; homology; inverse folding; STABILITY;
D O I
10.1089/cmb.2008.0202
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
The inverse protein folding problem is that of designing an amino acid sequence which has a prescribed native protein fold. This problem arises in drug design where a particular structure is necessary to ensure proper protein-protein interactions. Previously, tubular structures for a three-dimensional (3D) hexagonal prism lattice were introduced and their stability was formally proved for simple instances under the hydrophobic-polar (HP) model of Dill. In this article, we generalize the design of tubular structures to allow for much larger variety of designable structures by allowing branching of tubes. Our generalized design could be used to roughly approximate given 3D shapes in the considered lattice. Although the generalized tubular structures are not stable under the HP model, we can prove that a simple instance of generalized tubular structures is structurally stable (all native folds have the designed shape) under a refined version of the HP model, called the HPC model. We conjecture that there is a way to choose which hydrophobic monomers are cysteines in all generalized tubular structures such that the designed proteins are structurally stable under the HPC model.
引用
收藏
页码:769 / 802
页数:34
相关论文
共 12 条
  • [1] Long proteins with unique optimal foldings in the H-P model
    Aichholzer, O
    Bremner, D
    Demaine, ED
    Meijer, H
    Sacristán, V
    Soss, M
    [J]. COMPUTATIONAL GEOMETRY-THEORY AND APPLICATIONS, 2003, 25 (1-2): : 139 - 159
  • [2] Protein folding in the hydrophobic-hydrophilic (HP) model is NP-complete
    Berger, B
    Leighton, T
    [J]. JOURNAL OF COMPUTATIONAL BIOLOGY, 1998, 5 (01) : 27 - 40
  • [3] On the complexity of protein folding
    Crescenzi, P
    Goldman, D
    Papadimitriou, C
    Piccolboni, A
    Yannakakis, M
    [J]. JOURNAL OF COMPUTATIONAL BIOLOGY, 1998, 5 (03) : 423 - 465
  • [4] DOMINANT FORCES IN PROTEIN FOLDING
    DILL, KA
    [J]. BIOCHEMISTRY, 1990, 29 (31) : 7133 - 7155
  • [5] THEORY FOR THE FOLDING AND STABILITY OF GLOBULAR-PROTEINS
    DILL, KA
    [J]. BIOCHEMISTRY, 1985, 24 (06) : 1501 - 1509
  • [6] Gupta Arvind, 2007, Proceedings of the 2007 International Conference on Bioinformatics & Computational Biology. BIOCOMP 2007, P362
  • [7] Life and death of lymphocytes: A role in immunesenescence
    Gupta S.
    Su H.
    Bi R.
    Agrawal S.
    Gollapudi S.
    [J]. Immunity & Ageing, 2 (1)
  • [8] Prototeins
    Hayes, B
    [J]. AMERICAN SCIENTIST, 1998, 86 (03) : 216 - 221
  • [9] PROTEIN STABILITY AND MOLECULAR ADAPTATION TO EXTREME CONDITIONS
    JAENICKE, R
    [J]. EUROPEAN JOURNAL OF BIOCHEMISTRY, 1991, 202 (03): : 715 - 728
  • [10] Stable Structure-Approximating Inverse Protein Folding in 2D Hydrophobic-Polar-Cysteine (HPC) Model
    Khodabakhshi, Alireza Hadj
    Manuch, Jan
    Rafiey, Arash
    Gupta, Arvind
    [J]. JOURNAL OF COMPUTATIONAL BIOLOGY, 2009, 16 (01) : 19 - 30