DETERMINING PROTEIN LOOP CONFORMATION USING SCALING-RELAXATION TECHNIQUES

We recently developed a rapid loop closure algorithm in which bond lengths are scaled to constrain the ends of a segment to match a known distance and then gradually relaxed to their standard values, with boundary constraints maintained. Although the algorithm predicted the Zif286 zinc-finger loop to within approximately 2 angstrom, it had a serious limitation that made its more general use tentative: it omitted the atomic environment of the loop. Here we report an extension of the algorithm to take into account the protein environment surrounding a given loop from the outset of the conformational search and show that it predicts structure with an efficiency and accuracy that could not be achieved without continuous environmental inclusion. The algorithm should be widely applicable to structure determination when complete experimental information is unavailable.