A reduced representation of proteins for use in restraint satisfaction calculations

A reduced representation of proteins has been developed for use in restraint satisfaction calculations with dynamic simulated annealing. Each amino acid residue is represented by up to four spherical virtual atoms. The virtual bonds and excluded volume of these atoms has been parameterized by analysis of 83 protein structures determined at high resolution by X-ray crystallography. The use of the new representation in NOE distance restraint satisfaction has been compared with the standard all-atom representation for the determination of the structures of crambin, echistatin, and protein G. Using the reduced representation, there is a 30-fold decrease in the computer time needed for generating a single structure, and up to a 20-fold decrease in the time taken to produce an acceptable structure compared to using the all-atom representation. The root mean square deviation between the mean structure obtained with all-atom and reduced representations is between 1.5 and 1.7 A for C alpha atoms. The new representation is adequate for describing the "low-resolution" features of protein structure such as the general fold and the positions of secondary structure elements. It can also provide an initial structure for more detailed refinement with the full all-atom representation.