HYPER: a hierarchical algorithm for automatic determination of protein dihedral-angle constraints and stereospecific C beta H2 resonance assignments from NMR data.

Abstract

A new computer program, HYPER, has been developed for automated analysis of protein dihedral angle values and C beta H2 stereospecific assignments from NMR data. HYPER uses a hierarchical grid-search algorithm to determine allowed values of phi, psi, and chi 1 dihedral angles and C beta H2 stereospecific assignments based on a set of NMR-derived distance and/or scalar-coupling constraints. Dihedral-angle constraints are valuable for restricting conformational space and improving convergence in three-dimensional structure calculations. HYPER computes the set of phi, psi, and chi 1 dihedral angles and C beta H2 stereospecific assignments that are consistent with up to nine intraresidue and sequential distance bounds, two pairs of relative distance bounds, thirteen homo- and heteronuclear scalar coupling bounds, and two pairs of relative scalar coupling constant bounds. The program is designed to be very flexible, and provides for simple user modification of Karplus equations and standard polypeptide geometries, allowing it to accommodate recent and future improved calibrations of Karplus curves. The C code has been optimized to execute rapidly (0.3-1.5 CPU-sec residue-1 using a 5 degrees grid) on Silicon Graphics R8000, R10000 and Intel Pentium CPUs, making it useful for interactive evaluation of inconsistent experimental constraints. The HYPER program has been tested for internal consistency and reliability using both simulated and real protein NMR data sets.