CHARACTERIZATION OF CONFORMATIONAL PATTERNS IN ACTIVE AND INACTIVE FORMS OF KINASES USING PROTEIN BLOCKS APPROACH
The three-dimensional (3D) structure, which is critical for the function of a protein is usually conserved during evolution. It holds a wealth of information that can be harnessed to understand various aspects of proteins including sequence–structure–function–evolutionary relationships. The understanding of these complex relationships is facilitated by a simplistic one-dimensional (1D) representation of the tertiary structure like a string of letters.
The advantage is an easier visualization without losing much of the vital information due to dimension reduction. Using various methodologies, local structural patterns that can be combined to generate the desired backbone conformation have been identified that use atomic coordinates characterising 3D structures of proteins. Protein blocks (PBs) is a set of 16 such local structural descriptors, denoted by letters a… p that have been derived using unsupervised machine learning algorithms and can approximate the 3D space of proteins. Each letter corresponds to a pentapeptide with distinct values of eight dihedral angles (Φ,Ψ).
We demonstrate the use of PBs to characterize structural variations in enzymes using kinases as the case study. A protein kinase undergoes structural alterations as it switches to its active conformation ...