Predicting oligomeric assemblies:: N-mers a primer

被引:38
作者
Comeau, SR
Camacho, CJ
机构
[1] Univ Pittsburgh, Dept Computat Biol, Pittsburgh, PA 15261 USA
[2] Boston Univ, Bioinformat Grad Program, Boston, MA 02215 USA
关键词
macromolecules; supramolecular assembly; docking; complex prediction; oligomers;
D O I
10.1016/j.jsb.2005.03.006
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Multi-protein complexes play key roles in many biological processes. However, since the structures of these assemblies are hard to resolve experimentally, the detailed mechanism of how they work cooperatively in the cell has remained elusive. Similarly, recent advances on in silico prediction of protein-protein interactions have so far avoided this difficult problem. In this paper, we present a general algorithm to predict molecular assemblies of homo-oligomers. Given the number of N-mers and the 3D structure of one monomer, the method samples all the possible symmetries that N-mers can be assembled. Based on a scoring function that clusters the low free energy structures at each binding interface, the algorithm predicts the complex structure as well as the symmetry of the protein assembly. The method is quite general and does not involve any free parameters. The algorithm has been implemented as a public server and integrated to the protein-protein complex prediction server ClusPro. Using this application, we validated predictions for trimers, tetramers (discriminating between dimer of dimers and 4-fold symmetry structures), pentamers and hexamers (discriminating between trimer of dimers, dimer of trimers, and 6-fold symmetry structures), for a total of 107 assemblies. For 85%) of the multimers, the server predicts the complex structure within an average rms deviation of 2 angstrom from the full crystal. For complexes that involve more than one binding interface, the cluster size at each surface provides a strong indication as to which interface forms first. With improving scoring functions and computer power, our multimer docking approach could be used as a framework to address the more general problem of multi-protein assemblies. (c) 2005 Elsevier Inc. All rights reserved.
引用
收藏
页码:233 / 244
页数:12
相关论文
共 33 条
[1]   Construction of molecular assemblies via docking:: Modeling of tetramers with D2 symmetry [J].
Berchanski, A ;
Eisenstein, M .
PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS, 2003, 53 (04) :817-829
[2]   The Protein Data Bank [J].
Berman, HM ;
Westbrook, J ;
Feng, Z ;
Gilliland, G ;
Bhat, TN ;
Weissig, H ;
Shindyalov, IN ;
Bourne, PE .
NUCLEIC ACIDS RESEARCH, 2000, 28 (01) :235-242
[3]   Structure of a flavivirus envelope glycoprotein in its low-pH-induced membrane fusion conformation [J].
Bressanelli, S ;
Stiasny, K ;
Allison, SL ;
Stura, EA ;
Duquerroy, S ;
Lescar, J ;
Heinz, FX ;
Rey, FA .
EMBO JOURNAL, 2004, 23 (04) :728-738
[4]   CHARMM - A PROGRAM FOR MACROMOLECULAR ENERGY, MINIMIZATION, AND DYNAMICS CALCULATIONS [J].
BROOKS, BR ;
BRUCCOLERI, RE ;
OLAFSON, BD ;
STATES, DJ ;
SWAMINATHAN, S ;
KARPLUS, M .
JOURNAL OF COMPUTATIONAL CHEMISTRY, 1983, 4 (02) :187-217
[5]   Successful discrimination of protein interactions [J].
Camacho, CJ ;
Gatchell, DW .
PROTEINS-STRUCTURE FUNCTION AND GENETICS, 2003, 52 (01) :92-97
[6]   Protein-protein association kinetics and protein docking [J].
Camacho, CJ ;
Vajda, S .
CURRENT OPINION IN STRUCTURAL BIOLOGY, 2002, 12 (01) :36-40
[7]  
Camacho CJ, 2000, PROTEINS, V40, P525, DOI 10.1002/1097-0134(20000815)40:3<525::AID-PROT190>3.0.CO
[8]  
2-F
[9]  
CAMACHO CJ, 2005, BIOINFORMATICS
[10]  
CHUI W, 2002, CURR OPIN STRUC BIOL, V12, P263