7
Combinatories and Topology of theβ-Sandwich
andβ-Barrel Proteins
A.E. Kister, M.V. Kleyzit, T.I. Gelfand, and I.M. Gelfand
Summary.One of the main challenges in life science today is to understand how
genomic sequences determine geometric structure of proteins. Knowledge of the
three-dimensional structure provides valuable insights into functional properties of
proteins, since function of proteins is largely determined by their structure. The
ability to classify a genomic or amino acid sequence into its proper protein family,
and thereby to predict, to some degree of approximation, its structure and function
is an essential prerequisite to using genomic information for explaining enzymatic
processes that underlie cell behavior, understanding the molecular basis of disease,
and achieving rational drug design.
9.1 Introduction
With more than fifty complete genomes already sequenced, and at least a
hundred more close to completion [1], the gap between known sequences and
solved structures (collected at the Protein Data Bank [2] and classified in the
SCOP database [3]) is quickly widening. Consequently, the task of structure
prediction from amino acid sequence has taken center stage in the “postge-
nomic” era.
Direct approaches to structure determination include X-ray crystallogra-
phy, and nuclear magnetic resonance, among other techniques. However, such
methods are expensive, time consuming, and not always applicable.
The potential of alternative methods for protein comparison and classifica-
tion is not settled yet, and there is an urgent need for more reliable approaches
for such bioinformatics problems. Alternative approaches based on theoretical
study of the nature of the sequence/structure relationship can be immensely
useful in dealing with a wealth of data on newly sequenced genomic sequences.
Although it is more than 40 years since we know that all information re-
quired for the folding of a protein chain is contained in its amino acid sequence,
we have not yet learned how “to read” this text as to predict the detailed 3D
structure a protein whose sequence is known [4].