Lecture: Structural Bioinformatics 2

Aims

• To emphasise the modular structure of many proteins.
• To look at arrangements of protein secondary structure elements and how proteins can be classified according to their structure.
• To introduce the ways in which the stereochemical quality of a protein structure can be assessed.
• To introduce HSSP-curves and multiple alignments.

Objectives

After this lecture you will:

• be familiar with the criteria that are used in assessing the stereochemical quality of a protein;
• be aware of some common secondary structure motifs;
• be aware of factors that affect protein stability;
• be aware of modular proteins that contain combinations of domains in different structural contexts;
• understand how structural and functional clues can be inferred from multiple alignments;
• understand how sequence identity and structure similarity are related;
• be aware of alternative structural classification hierarchies, including SCOP and CATH.

Supplementary Material

The lecture handout contains some of the lecture slides.

Part I of Principles of Protein Structure, Comparative Protein Modelling and Visualisation contains a useful introduction to protein structure.

I recommend that you read the descriptions of the checks performed by PROCHECK, and that you look at some of the sample output produced by that program.

Peer Bork has collected some cartoons of modular extracellular proteins.

Structure and sequence divergence is discussed in:

• Chothia, C. and Lesk, A.M. (1986) The relation between the divergence of sequence and structure in proteins. EMBO J., 5, 823-826. (PubMed)

HSSP-curves were proposed by:

• Sander, C. and Schneider, R. Database of homology-derived protein structures and the structural meaning of sequence alignment. Proteins, 9, 56-68. (PubMed)

and were revised by:

• Rost, B. (1999) Twilight zone of protein sequence alignments. Protein Eng., 12, 85-94. (PubMed; colour figures and Appendix at Burkhard Rost's web site).

SCOP is a hierarchical structural classification of proteins. I recommend that you read the detailed description of SCOP.

CATH is a hierarchical classification of protein domain structures, which clusters proteins at four major levels, Class(C), Architecture(A), Topology(T) and Homologous superfamily (H). I recommend that you read the detailed description of CATH.