MAIN 98: STEPS TOWARDS AUTOMATIC MACROMOLECULAR STRUCTURE DETERMINATION

Dusan Turk

Jozef Stefan Institute Jamova 39 1 000 Ljubljana Slovenia (EUROPE) e-mail dusan.turk@ijs.si

MAIN development in the previous years encompassed routines for molecular models and electron density maps visualisation, molecular modeling, density modifications, structure refinement and analysis including kicked omit maps (a method to provide less model biased maps), map skeletonisation and more.

The next steps include integration of these routines into procedures which will gradually repace human manual work consisting of interactions with electron density maps and molecular models. Program assisted model rebuilding procedures are the first steps in this direction. Analysis tools can ``see'' where model seems inconsistent, new (omit) maps help to unreveal the mess, map skeletons lay the routes to which model is fitted. To make this possible a new energy term called 'skeleton attraction', which measures the fit of a molecular model to a skeleton, was added to the list of classical energy terms (bond, angle, dihedral, improper, electrostatic, VdW, hydrogen bonds, map correlations).

Refinement routines are this year reacher for reciprocal space weighted energy term and are based on fast cooling procedures of coordinates and B-values. Fast cooled refinement is konjugated gradient based minimization of randomly displaced coordinates and atomic B-values, where the size of the starting displacement is gradually lowered. Fast cooling enables in contrast to simulauted anealing (slow cooling) interactively driven refinement and can be therefore applied during model building. Interactivity is limited to reasonable sized proteins (up to 800 residues) on a moderate workstations.