Modeling in biological chemistry.From biochemical kinetics to systems biology

摘要

A brief review on biochemical kinetics in the twentieth century mainly concerned with enzyme kinetics and cooperative processes is presented.Molecular biology and,in particular,structural biology provided the basis for modeling biological phenomena at the molecular level.Structure was recognized as the ultimate and only level at which biological processes find an explanation that is satisfactory for chemists and physicists.A new epoch in biology was initiated by successful extensions of the molecular approach from individual molecules and reactions to the cellular and organismic level.Starting with sequencing of whole genomes in the 1980s more and more techniques became available that are suitable for upscaling from molecules to cells.A series of research programs was initiated:genomics dealing with sequencing the DNA of whole organisms,proteomics considering all proteins of a cell and their interactions,metabolomics studying all metabolic reactions of a cell or an organism,and functional genomics or systems biology aiming at an exploration of the dynamics of complete biological entities.At the same time computational facilities have experienced an unexpected development in speed of calculations and storing devices.At present computer simulations of whole cells at molecular resolution are within reach.The challenge for the theorist in biology is to develop methods for handling the enormously complex networks of gene regulation and metabolism in such a way that biological questions can be addressed.This goal cannot be achieved by dynamical systems theory alone.What is needed is a joint effort from different mathematical disciplines supported by empirical knowledge and tools from discrete mathematics to informatics.Two sections with selected examples from our own laboratory dealing with structural bioinformatics of RNA and with a dynamical systems approach to gene regulation are added.