HYPER: A hierarchical algorithm for automatic determination of protein dihedral-angle constraints and stereospecific (CH2)-H-beta resonance assignments from NMR data

A new computer program, HYPER, has been developed for automated analysis of protein dihedral angle values and (CH2)-H-beta 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 (CH2)-H-beta st ereospecific assignments based on a set of NMR-derived distance and/or scal ar-coupling constraints. Dihedral-angle constraints are valuable for restri cting conformational space and improving convergence in three-dimensional s tructure calculations. HYPER computes the set of phi, Psi, and chi(1)dihedr al angles and (CH2)-H-beta stereospecific assignments that are consistent w ith up to nine intraresidue and sequential distance bounds, two pairs of re lative distance bounds, thirteen homo- and heteronuclear scalar coupling bo unds, and two pairs of relative scalar coupling constant bounds. The progra m is designed to be very flexible, and provides for simple user modificatio n 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) u sing a 5 degrees grid) on Silicon Graphics R8000, R10000 and Intel Pentium CPUs, making it useful for interactive evaluation of inconsistent experimen tal constraints. The HYPER program has been tested for internal consistency and reliability using both simulated and real protein NMR data sets.