Conformational search by potential energy annealing: Algorithm and application to cyclosporin A

Abstract
A major problem in modelling (biological) macromolecules is the search for low-energy conformations. The complexity of a conformational search problem increases exponentially with the number of degrees of freedom which means that a systematic search can only be performed for very small structures. Here we introduce a new method (PEACS) which has a far better performance than conventional search methods. To show the advantages of PEACS we applied it to the refinement of Cyclosporin A and compared the results with normal molecular dynamics (MD) refinement. The structures obtained with PEACS were lower in energy and agreed with the NMR parameters much better than those obtained with MD. From the results it is further clear that PEACS samples a much larger part of the available conformational space than MD does.