结构生物学sturcture biology explore-19.pdfVIP

176 Steady progress has been made in the field of ab initio protein folding. A variety of methods now allow the prediction of low-resolution structures of small proteins or protein fragments up to approximately 100 amino acid residues in length. Such low-resolution structures may be sufficient for the functional annotation of protein sequences on a genome-wide scale. Although no consistently reliable algorithm is currently available, the essential challenges to developing a general theory or approach to protein structure prediction are better understood. The energy landscapes resulting from the structure prediction algorithms are only partially funneled to the native state of the protein. This review focuses on two areas of recent advances in ab initio structure prediction — improvements in the energy functions and strategies to search the caldera region of the energy landscapes. Addresses *Center for Biophysics and Computational Biology, University of Illinois, 600 South Mathews Avenue, Urbana, Illinois 61801, USA ?School of Chemical Sciences, University of Illinois, 600 South Mathews Avenue, Urbana, Illinois 61801, USA Current Opinion in Structural Biology 2002, 12:176–181 0959-440X/02/$ — see front matter ? 2002 Elsevier Science Ltd. All rights reserved. Abbreviations CASP Critical Assessment of Structure Prediction PDB Protein Data Bank rmsd root mean square deviation UNRES united residue Introduction The prediction of a protein’s structure and folding mechanism from knowledge only of its amino acid sequence has been described as the determination of the second half of the genetic code [1]. Because of its importance for both practical and theoretical purposes, this challenge has been steadily pursued for over a decade, a pursuit that has yielded a wide variety of novel computational techniques and much progress. The approaches used to predict protein structure range from comparative modeling using a homologous protein that already exists in the structural dat