Enhanced genome annotation using structural profiles in the program 3D-PSSM

A method (three-dimensional position-specific scoring matrix, 3D-PSSM) to r ecognise remote protein sequence homologues is described. The method combin es the power of multiple sequence profiles with knowledge of protein struct ure to provide enhanced recognition and thus functional assignment of newly sequenced genomes. The method uses structural alignments of homologous pro teins of similar three-dimensional structure in the structural classificati on of proteins (SCOP) database to obtain a structural equivalence of residu es. These equivalences are used to extend multiply aligned sequences obtain ed by standard sequence searches. The resulting large superfamily-based mul tiple alignment is converted into a PSSM. Combined with secondary structure matching and solvation potentials, 3D-PSSM can recognise structural and fu nctional relationships beyond state-of-the-art sequence methods. In a cross -validated benchmark on 136 homologous relationships unambiguously undetect able by position-specific iterated basic local alignment search tool (PSI-B last), 3D-PSSM can confidently assign 18 %. The method was applied to the r emaining unassigned regions of the Mycoplasma genitalium genome and an addi tional 13 regions were assigned with 95 % confidence. 3D-PSSM is available to the community as a web server: http://www.bmm.icnet.uk/servers;/3dpssm (C) 2000 Academic Press.