Multiple-copy simultaneous search

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]. 

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. 

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. 

A target site is characterized by different descriptors which can be used to orient a ligand in the site. Site characterization can be divided into two classes, based upon their use of geometric features and chemical functionality. Many programs have been developed we describe two examples to illustrate the different ideas SPHGEN (from the DOCK suite of programs) and Multiple Copy Simultaneous Search (MCSS). ... 

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