Rotamers - to be or not to be? Analysis of amino acid side chain conformations in globular proteins. Side chains, regular backbone conformation, protein crystal structures

In this work the distribution of side-chain conformations in protein crystal structures is analyzed. Large deviations from rotameric #chi#-values occur systematically and cannot be attributed merely to errors in crystal structure determination. The 'rotamericity' (the fraction of residues within #+-# 20"0 of the x-angles of a rotamer) not only remains substantially below 100% (70-95% for various amino acids) with improving crystallographic resolution but actually decreases for 7 out of 17 amino acid types after a critical resolution limit is crossed. This effect has been observed for external as well as for internal residues. The rotamericity depends essentially on the different environments the amino acid meets in real protein structures. Factors such as the backbone torsion angles of the residue itself, the secondary structure and tertiary contacts influence the rotamericity. Correlations with physical properties describing volume, extension, flexibility, polarity and hydrophobicity of the side chain are shown. A substantial number of amino acid-chains are under strain. Obviously, the relaxation of some side chains is sacrified for a global minimum of free energy to be achieved at a higher organizational level involving the protein fold. The results are relevant for the development of algorithms that model proteins using restricted scanning of the torsion angle space. (WEN)Available from TIB Hannover: D.Dt.F.QN1(2,10) / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekSIGLEBundesministerium fuer Forschung und Technologie (BMFT), Bonn (Germany)DEGerman