DETERMINING PROTEIN LOOP CONFORMATION USING SCALING-RELAXATION TECHNIQUES

We recently developed a rapid loop closure algorithm in which bond len gths are scaled to constrain the ends of a segment to match a known di stance and then gradually relaxed to their standard values, with bound ary constraints maintained. Although the algorithm predicted the Zif28 6 zinc-finger loop to within approximately 2 angstrom, it had a seriou s limitation that made its more general use tentative: it omitted the atomic environment of the loop. Here we report an extension of the alg orithm to take into account the protein environment surrounding a give n loop from the outset of the conformational search and show that it p redicts structure with an efficiency and accuracy that could not be ac hieved without continuous environmental inclusion. The algorithm shoul d be widely applicable to structure determination when complete experi mental information is unavailable.