New approaches in molecular structure prediction

In the past years, much effort has been put on the development of new methodologies and algorithms for the prediction of protein secondary and tertiary structures from (sequence) data; this is reviewed in detail. New approaches for these predictions such as neural network methods, genetic algorithms, machine learning, and graph theoretical methods are discussed. Secondary structure prediction algorithms were improved mostly by considering families of related proteins; however, for the reliable tertiary structure modeling of proteins, knowledge-based techniques are still preferred. Methods and examples with more or less successful results are described. Also, programs and parameterizations for energy minimisations, molecular dynamics, and electrostatic interactions have been improved, especially with respect to their former limits of applicability. Other topics discussed in this review include the use of traditional and on-line databases, the docking problem and surface properties of biomolecules, packing of protein cores, de novo design and protein engineering, prediction of membrane protein structures, the verification and reliability of model structures, and progress made with currently available software and computer hardware. In summary, the prediction of the structure, function, and other properties of a protein is still possible only within limits, but these limits continue to be moved.