Introduction

Several applications in biology - e.g., incorporation of protein flexibility in ligand docking algorithms, interpretation of fuzzy X-ray crystallographic data, and homology modeling - require computing the internal parameters of a flexible fragment (usually, a loop) of a protein in order to connect its termini to the rest of the protein without causing any steric clash. One must often sample many such conformations in order to explore and adequately represent the conformational range of the studied loop. While sampling must be fast, it is made difficult by the fact that two conflicting constraints - kinematic closure and clash avoidance - must be satisfied concurrently. This paper describes two efficient and complementary sampling algorithms to explore the space of closed clash-free conformations of a flexible protein loop. The "seed sampling" algorithm samples broadly from this space, while the "deformation sampling" algorithm uses seed conformations as starting points to explore the conformation space around them at a finer grain. Computational results are presented for various loops ranging from 5 to 25 residues. More specific results also show that the combination of the sampling algorithms with a functional site prediction software (FEATURE) makes it possible to compute and recognize calcium-binding loop conformations. The sampling algorithms are implemented in a toolkit (LoopTK), which is available at https://simtk.org/home/looptk.

Publications

  1. Efficient algorithms to explore conformation spaces of flexible protein loops.
    Cite this
    Yao P, Dhanik A, Marz N, Propper R, Kou C, Liu G, van den Bedem H, Latombe JC, Halperin-Landsberg I, Altman RB, 2008-10-01 - IEEE/ACM transactions on computational biology and bioinformatics

Credits

  1. Peggy Yao
    Developer

    Computer Science Department, Stanford University

  2. Ankur Dhanik
    Developer

  3. Nathan Marz
    Developer

  4. Ryan Propper
    Developer

  5. Charles Kou
    Developer

  6. Guanfeng Liu
    Developer

  7. Henry van den Bedem
    Developer

  8. Jean-Claude Latombe
    Developer

  9. Inbal Halperin-Landsberg
    Developer

  10. Russ Biagio Altman
    Investigator

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Summary
AccessionBT002283
Tool TypeApplication
Category
PlatformsLinux/Unix
TechnologiesC++
User InterfaceTerminal Command Line
Download Count0
Submitted ByRuss Biagio Altman