Drug discovery using grid technology

A number of computer resources, such as CPUs and storages, can be connected over networks to construct a huge virtual computing environment using grid technologies. Our project "g-Drug Discovery" aims to develop a platform for drug discovery using grid technologies, on which various analysis and calculations are conducted, such as molecular mechanics method, replica exchange method, docking with proteins, molecular orbital method, and 3-dimensional quantitative structure activity relationship. For this aim we have specified a markup language for drug discovery (DrugML) and constructed database system. In this note we report some results of a ligand-receptor docking simulation, which is calculated on this platform using a grid RPC system "OmniRPC" and virtual screening software "Xsi" (ku-su-shi). We assume only 2-dimensional structure of ligand and 3-dimensional structure of receptor, and reproduce the complex of these molecules.

[1]  Eric Schwegler,et al.  Linear scaling computation of the Fock matrix , 1997 .

[2]  Eiji Osawa,et al.  Corner flapping: a simple and fast algorithm for exhaustive generation of ring conformations , 1989 .

[3]  N. Skelton,et al.  Tryptophan zippers: Stable, monomeric β-hairpins , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[4]  Ching-Hsing Yu,et al.  Ab Initio Geometry Determinations of Proteins. 1. Crambin , 1998 .

[5]  Noriyuki Kurita,et al.  Molecular orbital analysis based on fragment molecular orbital scheme , 2003 .

[6]  H. Goto.  A revised nomenclature for the ring conformation and a note on the conformational distance in cyclododecane , 1992 .

[7]  John W. R. Schwabe,et al.  The crystal structure of the estrogen receptor DNA-binding domain bound to DNA: How receptors discriminate between their response elements , 1993, Cell.

[8]  K. Kitaura,et al.  Definition of molecular orbitals in fragment molecular orbital method , 2002 .

[9]  Carmay Lim,et al.  Factors governing the protonation state of cysteines in proteins: an Ab initio/CDM study. , 2002, Journal of the American Chemical Society.

[10]  L. Nilsson,et al.  Structural and dynamic differences of the estrogen receptor DNA-binding domain, binding as a dimer and as a monomer to DNA: molecular dynamics simulation studies , 1999, European Biophysics Journal.

[11]  Masami Uebayasi,et al.  Pair interaction molecular orbital method: an approximate computational method for molecular interactions , 1999 .

[12]  Fumitoshi Sato,et al.  Calculation of all-electron wavefunction of hemoprotein cytochrome c by density functional theory , 2001 .

[13]  Hitoshi Gotō.  A frontier mode-following method for mapping saddle points of conformational interconversion in flexible molecules starting from the energy minimum , 1998 .

[14]  Ben L. Feringa,et al.  Chemistry of Unique Chiral Olefins. 4. Theoretical Studies of the Racemization Mechanism of trans- and cis-1,1',2,2',3,3',4,4'-Octahydro-4,4'-biphenanthrylidenes. , 1999, The Journal of organic chemistry.

[15]  K. Nakanishi,et al.  Circular dichroic spectroscopy : exciton coupling in organic stereochemistry , 1983 .

[16]  K. Kitaura,et al.  Fragment molecular orbital method: an approximate computational method for large molecules , 1999 .

[17]  Mitsuhisa Sato,et al.  OmniRPC: a grid RPC system for parallel programming in cluster and grid environment , 2003, CCGrid 2003. 3rd IEEE/ACM International Symposium on Cluster Computing and the Grid, 2003. Proceedings..

[18]  C. Robinson,et al.  Metal-dependent folding and stability of nuclear hormone receptor DNA-binding domains. , 2002, Journal of molecular biology.

[19]  Laxmikant V. Kale,et al.  NAMD2: Greater Scalability for Parallel Molecular Dynamics , 1999 .

[20]  Yuto Komeiji,et al.  Fragment molecular orbital method: analytical energy gradients , 2001 .

[21]  Noriyuki Kurita,et al.  Fragment molecular orbital method with density functional theory and DIIS convergence acceleration , 2003 .

[22]  Mitsuhisa Sato,et al.  OmniRPC: A Grid RPC Facility for Cluster and Global Computing in OpenMP , 2001, WOMPAT.

[23]  Paola Gramatica,et al.  New 3D Molecular Descriptors: The WHIM theory and QSAR Applications , 2002 .

[24]  Kaori Fukuzawa,et al.  Fragment molecular orbital method: use of approximate electrostatic potential , 2002 .

[25]  Marina Lasagni,et al.  New molecular descriptors for 2D and 3D structures. Theory , 1994 .