Search multiple-copy

To overcome the limitations of the database search methods, conformational search methods were developed [95,96,109]. There are many such methods, exploiting different protein representations, objective function tenns, and optimization or enumeration algorithms. The search algorithms include the minimum perturbation method [97], molecular dynamics simulations [92,110,111], genetic algorithms [112], Monte Carlo and simulated annealing [113,114], multiple copy simultaneous search [115-117], self-consistent field optimization [118], and an enumeration based on the graph theory [119]. 

Errors in instrumentation calibration have been reduced by 90 percent due to the elimination of multiple, outdated copies of calibration procedures/data sheets. An instrument mechanic can now get the current specification from a single, up-to-date source whenever a work order is received. The time wasted in searching multiple files has been eliminated. 

Miranker A, Karplus M. Functionality maps of binding sites a multiple copy simultaneous search method. Proteins 1991 11 29-34. 

II. Docking Molecular Fragments A Multiple Copy Simultaneous Search... 

A somewhat different approach has been implemented in MCSS (multiple copies simultaneous search) [10]. In this method, up to 5000 copies of a functional group are randomly distributed in the binding pocket and simultaneously minimized by a force field. The simultaneous optimization is performed in... 

Joseph-McCarthy, D., Hogle, J. M. and Karplus, M. (1997). Use of the multiple copy simultaneous search (MCSS) method to design a new class of picomavirus capsid binding drugs. Proteins, 29, 32-58. 

It is possible, as shown by Rossmann and Blow (1962), to search for redundancies in Patterson space that correspond to the multiple copies of molecular transforms. Rossmann and Blow show, however, that the Patterson map does not need to be computed and used in any graphical sense, but that an equivalent search process can be carried out directly in diffraction or reciprocal space. Using such a search procedure, called a rotation function, they showed that noncrystallographic relationships, both proper and improper rotations, could be deduced in many cases directly from the X-ray intensity data alone, and in the complete absence of phase information. Translational relationships (only after rotations have been established) can also be deduced by a similar approach. Rotation functions and translation functions constitute what we call molecular replacement procedures. Ultimately the spatial relationships among multiple molecules in an asymmetric unit can be defined by their application. 

Caflisch A, Miranker A, Karplus M (1993) Multiple copy simultaneous search and construction of ligands in binding sites application to inhibitors of HIV-1 aspartic proteinase. J Med Chem 36 2142-2167... 

Miranker A and M Karplus 1991. Functionality Maps of Binding Sites - A Multiple Copy Simultaneous Search Method. Proteins Structure, Function and Genetics 11 29-34. 

The solution to the rigid body problem was to set the values of internal force constant to very large values and use fragments with no torsional degrees of freedom. To treat protein flexibility, a time-dependent Hartree (TDH) approximation is used to normalize the forces on the protein to that of a single fragment. Caflisch et al. >4 applied the multiple-copy, simultaneous search... 

A. Caflisch, A. Miranker, and M. Karplus, J. Med. Chem., 36, 2142 (1993). Multiple Copy Simultaneous Search and Construction of Ligands in Binding Sites Applications to Inhibitors of HlV-1 Aspartic Proteinase. 

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