Iterative cluster-NMA: A tool for generating conformational transitions in proteins.
نویسندگان
چکیده
Computational models provide insight into the structure-function relationship in proteins. These approaches, especially those based on normal mode analysis, can identify the accessible motion space around a given equilibrium structure. The large magnitude, collective motions identified by these methods are often well aligned with the general direction of the expected conformational transitions. However, these motions cannot realistically be extrapolated beyond the local neighborhood of the starting conformation. In this article, the iterative cluster-NMA (icNMA) method is presented for traversing the energy landscape from a starting conformation to a desired goal conformation. This is accomplished by allowing the evolving geometry of the intermediate structures to define the local accessible motion space, and thus produce an appropriate displacement. Following the derivation of the icNMA method, a set of sample simulations are performed to probe the robustness of the model. A detailed analysis of beta1,4-galactosyltransferase-T1 is also given, to highlight many of the capabilities of icNMA. Remarkably, during the transition, a helix is seen to be extended by an additional turn, emphasizing a new unknown role for secondary structures to absorb slack during transitions. The transition pathway for adenylate kinase, which has been frequently studied in the literature, is also discussed.
منابع مشابه
cNMA: a framework of encounter complex-based normal mode analysis to model conformational changes in protein interactions
MOTIVATION It remains both a fundamental and practical challenge to understand and anticipate motions and conformational changes of proteins during their associations. Conventional normal mode analysis (NMA) based on anisotropic network model (ANM) addresses the challenge by generating normal modes reflecting intrinsic flexibility of proteins, which follows a conformational selection model for ...
متن کاملDeciphering conformational transitions of proteins by small angle X-ray scattering and normal mode analysis.
Structural flexibility and conformational rearrangements are often related to important functions of biological macromolecules, but the experimental characterization of such transitions with high-resolution techniques is challenging. At a lower resolution, small angle X-ray scattering (SAXS) can be used to obtain information on biomolecular shapes and transitions in solution. Here, we present S...
متن کاملAn NMA-guided path planning approach for computing large-amplitude conformational changes in proteins.
This paper presents a new method for computing macromolecular motions based on the combination of path planning algorithms, originating from robotics research, and elastic network normal mode analysis. The low-frequency normal modes are regarded as the collective degrees of freedom of the molecule. Geometric path planning algorithms are used to explore these collective degrees of freedom in ord...
متن کاملShape-Dependent Global Deformation Modes of Large Protein Structures.
Conformational changes are central to the functioning of pore-forming proteins that open and close their molecular gates in response to external stimuli such as pH, ionic strength, membrane voltage or ligand binding. Normal mode analysis (NMA) is used to identify and characterize the slowest motions in the gA, KcsA, ClC-ec1, LacY and LeuT(Aa) proteins at the onset of gating. Global deformation ...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
عنوان ژورنال:
- Proteins
دوره 74 3 شماره
صفحات -
تاریخ انتشار 2009