A self-organizing algorithm for modeling protein loops. 2009

Pu Liu, and Fangqiang Zhu, and Dmitrii N Rassokhin, and Dimitris K Agrafiotis
Johnson & Johnson Pharmaceutical Research and Development, Exton, Pennsylvania, USA. pliu24@its.jnj.com

Protein loops, the flexible short segments connecting two stable secondary structural units in proteins, play a critical role in protein structure and function. Constructing chemically sensible conformations of protein loops that seamlessly bridge the gap between the anchor points without introducing any steric collisions remains an open challenge. A variety of algorithms have been developed to tackle the loop closure problem, ranging from inverse kinematics to knowledge-based approaches that utilize pre-existing fragments extracted from known protein structures. However, many of these approaches focus on the generation of conformations that mainly satisfy the fixed end point condition, leaving the steric constraints to be resolved in subsequent post-processing steps. In the present work, we describe a simple solution that simultaneously satisfies not only the end point and steric conditions, but also chirality and planarity constraints. Starting from random initial atomic coordinates, each individual conformation is generated independently by using a simple alternating scheme of pairwise distance adjustments of randomly chosen atoms, followed by fast geometric matching of the conformationally rigid components of the constituent amino acids. The method is conceptually simple, numerically stable and computationally efficient. Very importantly, additional constraints, such as those derived from NMR experiments, hydrogen bonds or salt bridges, can be incorporated into the algorithm in a straightforward and inexpensive way, making the method ideal for solving more complex multi-loop problems. The remarkable performance and robustness of the algorithm are demonstrated on a set of protein loops of length 4, 8, and 12 that have been used in previous studies.

UI MeSH Term Description Entries
D008956 Models, Chemical Theoretical representations that simulate the behavior or activity of chemical processes or phenomena; includes the use of mathematical equations, computers, and other electronic equipment. Chemical Models,Chemical Model,Model, Chemical
D008958 Models, Molecular Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures. Molecular Models,Model, Molecular,Molecular Model
D011487 Protein Conformation The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. PROTEIN STRUCTURE, QUATERNARY describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain). Conformation, Protein,Conformations, Protein,Protein Conformations
D011506 Proteins Linear POLYPEPTIDES that are synthesized on RIBOSOMES and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of AMINO ACIDS determines the shape the polypeptide will take, during PROTEIN FOLDING, and the function of the protein. Gene Products, Protein,Gene Proteins,Protein,Protein Gene Products,Proteins, Gene
D000465 Algorithms A procedure consisting of a sequence of algebraic formulas and/or logical steps to calculate or determine a given task. Algorithm
D018360 Crystallography, X-Ray The study of crystal structure using X-RAY DIFFRACTION techniques. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed) X-Ray Crystallography,Crystallography, X Ray,Crystallography, Xray,X Ray Crystallography,Xray Crystallography,Crystallographies, X Ray,X Ray Crystallographies
D019295 Computational Biology A field of biology concerned with the development of techniques for the collection and manipulation of biological data, and the use of such data to make biological discoveries or predictions. This field encompasses all computational methods and theories for solving biological problems including manipulation of models and datasets. Bioinformatics,Molecular Biology, Computational,Bio-Informatics,Biology, Computational,Computational Molecular Biology,Bio Informatics,Bio-Informatic,Bioinformatic,Biologies, Computational Molecular,Biology, Computational Molecular,Computational Molecular Biologies,Molecular Biologies, Computational
D030562 Databases, Protein Databases containing information about PROTEINS such as AMINO ACID SEQUENCE; PROTEIN CONFORMATION; and other properties. Amino Acid Sequence Databases,Databases, Amino Acid Sequence,Protein Databases,Protein Sequence Databases,SWISS-PROT,Protein Structure Databases,SwissProt,Database, Protein,Database, Protein Sequence,Database, Protein Structure,Databases, Protein Sequence,Databases, Protein Structure,Protein Database,Protein Sequence Database,Protein Structure Database,SWISS PROT,Sequence Database, Protein,Sequence Databases, Protein,Structure Database, Protein,Structure Databases, Protein

Related Publications

Pu Liu, and Fangqiang Zhu, and Dmitrii N Rassokhin, and Dimitris K Agrafiotis
January 2006, Nucleic acids research,
Pu Liu, and Fangqiang Zhu, and Dmitrii N Rassokhin, and Dimitris K Agrafiotis
December 1989, Proceedings of the National Academy of Sciences of the United States of America,
Pu Liu, and Fangqiang Zhu, and Dmitrii N Rassokhin, and Dimitris K Agrafiotis
May 2007, Journal of computational chemistry,
Pu Liu, and Fangqiang Zhu, and Dmitrii N Rassokhin, and Dimitris K Agrafiotis
April 2008, Journal of computational chemistry,
Pu Liu, and Fangqiang Zhu, and Dmitrii N Rassokhin, and Dimitris K Agrafiotis
January 2000, IEEE transactions on neural networks,
Pu Liu, and Fangqiang Zhu, and Dmitrii N Rassokhin, and Dimitris K Agrafiotis
March 2006, IEEE transactions on neural networks,
Pu Liu, and Fangqiang Zhu, and Dmitrii N Rassokhin, and Dimitris K Agrafiotis
September 2015, IEEE transactions on image processing : a publication of the IEEE Signal Processing Society,
Pu Liu, and Fangqiang Zhu, and Dmitrii N Rassokhin, and Dimitris K Agrafiotis
April 2014, IEEE transactions on cybernetics,
Pu Liu, and Fangqiang Zhu, and Dmitrii N Rassokhin, and Dimitris K Agrafiotis
January 2006, Neural networks : the official journal of the International Neural Network Society,
Pu Liu, and Fangqiang Zhu, and Dmitrii N Rassokhin, and Dimitris K Agrafiotis
September 2010, IEEE transactions on neural networks,
Copied contents to your clipboard!