Kuntz I, Blaney J, Oatley S, Langridge R. Ferrin T. A geometric approach to macromolecule-ligand interactions. Journal of Molecular Biology 1982; 161:269--288.  Home/Search   Document Not in Database   Summary   Related Articles   Check

....that it is possible for the network to generate code rapidly and in a manner that can never be known apriorifor every possible condition. The inspiration for a genetic algorithm based approach to solution composition comes from nature in the form of the docking problem in molecular biology [4], 5] 6] Solutions that efficiently match a particular fault should be able to dock with the fault. Prediction for successful docking in biology can be attempted by searching for minimal energy or minimal geometric construction combinations. Here we consider a genetic algorithm used to ....

I. Kuntz, J. Blaney, S. Oatley, R. Langridge, and T. Ferrin, "A geometric approach to macromolecule-ligand interactions," Journal of Molecular Biology, 1982.

....the key programs in the dock suite is depicted in Figure 4. The receptor coordinates at the top represent 3D structure of protein. The molecular modeller identifies the active site, and other sites of interest, and uses the program sphgen to generate the sphere centers, which fill the site [13]. The program grid generates the scoring grids [14] The program dock matches spheres (generated by sphgen) with ligand atoms and uses scoring grids (from grid) to evaluate ligand orientations [13] 14] It also minimizes energy based scores [15] 6] The focus of our work is on docking ....

.... of interest, and uses the program sphgen to generate the sphere centers, which fill the site [13] The program grid generates the scoring grids [14] The program dock matches spheres (generated by sphgen) with ligand atoms and uses scoring grids (from grid) to evaluate ligand orientations [13] [14] It also minimizes energy based scores [15] 6] The focus of our work is on docking molecules in CDB with receptor to identify potential compounds that can act as drug . Hence, discussion in this paper is centered on the execution of the program dock as parameter sweep application on ....

I. Kuntz, J. Blaney, S. Oatley, R. Langridge, and T. Ferrin, A geometric approach to macromolecule-ligand interactions, Journal of Molecular Biology, 161: 269-288, 1982.

....the dock suite is depicted in Figure 4. The receptor coordinates at the top represent the three dimensional (3D) structure of a protein. The molecular modeller identifies the active site, and other sites of interest, and uses the program sphgen to generate the sphere centers, which fill the site [14] . The program grid generates the scoring grids [15] The program dock matches spheres (generated by sphgen) with ligand atoms and uses scoring grids (from grid) to evaluate ligand orientations [14] 15] It also minimizes energy based scores [16] 6] The focus of our work is on docking ....

.... sites of interest, and uses the program sphgen to generate the sphere centers, which fill the site [14] The program grid generates the scoring grids [15] The program dock matches spheres (generated by sphgen) with ligand atoms and uses scoring grids (from grid) to evaluate ligand orientations [14] [15] It also minimizes energy based scores [16] 6] The focus of our work is on docking molecules in CDB with receptor to identify potential compounds that act as a drug. Hence, discussion in this paper is centered on the execution of the program dock as parameter sweep application on ....

I. Kuntz, J. Blaney, S. Oatley, R. Langridge, and T. Ferrin, A geometric approach to macromolecule-ligand interactions, Journal of Molecular Biology, 161: 269-288, 1982.

....the key programs in the dock suite is depicted in Figure 4. The receptor coordinates at the top represent 3D structure of protein. The molecular modeller identifies the active site, and other sites of interest, and uses the program sphgen to generate the sphere centers, which fill the site [13]. The program grid generates the scoring grids [14] The program dock matches spheres (generated by sphgen) with ligand atoms and uses scoring grids (from grid) to evaluate ligand orientations [13] 14] It also minimizes energy based scores [15] 6] The focus of our work is on docking ....

.... of interest, and uses the program sphgen to generate the sphere centers, which fill the site [13] The program grid generates the scoring grids [14] The program dock matches spheres (generated by sphgen) with ligand atoms and uses scoring grids (from grid) to evaluate ligand orientations [13] [14] It also minimizes energy based scores [15] 6] The focus of our work is on docking molecules in CDB with receptor to identify potential compounds that can act as drug . Hence, discussion in this paper is centered on the execution of the program dock as parameter sweep application on ....

I. Kuntz, J. Blaney, S. Oatley, R. Langridge, and T. Ferrin, A geometric approach to macromolecule-ligand interactions, Journal of Molecular Biology, 161: 269-288, 1982.

....based on energy minimization (refs. 1 6 of [55] were only partially successful. Geometric approaches (refs. 7 16 of [55] including [25] were much more successful, but (at least the earlier ones) were not reliable enough and suffered from unacceptably long computation time [55] Kuntz et al. [60] transform the structures of the ligand and of the receptor of two proteins into a graph in which they search for four cliques. Each detected clique is mapped into a three dimensional transformation and checked for possible penetration of the ligand into the receptor, in which case it is rejected. ....

I.D. Kuntz, J.M. Blaney, S.J. Oatley, R. Langridge, and T.E. Ferrin, "A Geometric Approach to Macromolecule-Ligand Interactions," J. Molecular Biology, vol. 161, pp. 269-288, 1982.

....a certain type of features, are pose clustering [30] alignment [19] and, of course, geometric hashing. A comparison between these techniques is found in [31] Many other works have addressed the problem; see [3, 5, 6, 8, 10, 13, 17, 18, 27] for studies in the context of object recognition, and [1, 12, 14, 20, 22, 24, 26, 28] for studies in the context of molecular biology. Most of these works have various limitations, some of which are quite severe. They either restrict the shape of the matched objects, or assume that there is no occlusion, or handle only restricted motions. The methods that do not have these ....

I.D. Kuntz, J.M. Blaney, S.J. Oatley, R. Langridge, and T.E. Ferrin, A geometric approach to macromolecule-ligand interactions, J. of Molecular Biology, 161 (1982) 269--288.

....based on energy minimization (refs. 1 6 of [55] were only partially successful. Geometric approaches (refs. 7 16 of [55] including [25] were much more successful, but (at least the earlier ones) were not reliable enough and suffered from unacceptably long computation time [55] Kuntz et al. [60] transform the structures of the ligand and of the receptor of two proteins into a graph in which they search for four cliques. Each detected clique is mapped into a three dimensional transformation and checked for possible penetration of the ligand into the receptor, in which case it is rejected. ....

I.D. Kuntz, J.M. Blaney, S.J. Oatley, R. Langridge, and T.E. Ferrin, "A Geometric Approach to Macromolecule-Ligand Interactions," J. Molecular Biology, vol. 161, pp. 269-288, 1982.

....As our method is general and is not restricted to a particular molecular surface representation, our choices of surface descriptions further facilitate handling flexibility in either of the molecules. We have experimented with two types of surface representations, that of Kuntz et al. [55], and that of Lin et al. 56, 57] Both surface descriptions are derived from the solvent accessible surface generated by Connolly [58, 59] as defined by Richards [60] Both surface descriptions have been employed, and results from both are given below. The attractive surface description devised ....

....A detailed description of our two phase method is given below. These are divided into steps to clarify the exposition. A 2 D illustration of the two basic phases of the algorithm is depicted in Fig. 3. Preprocessing (1) The ligand molecule (model) is represented as a set of interest points [55, 56, 57]. 2) The (known) hinge position is picked as the origin of a 3 D Cartesian coordinate frame, which will be called the ligand frame . The orientation of this frame is set arbitrarily. 3) For each non ordered non collinear triplet of interest points in each ligand part, we define a unique ....

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I.D. Kuntz, J.M. Blaney, S.J. Oatley, R. Langridge, and T.E. Ferrin. A geometric approach to macromolecule-ligand interactions. J. Mol. Biol., 161:269--288, 1982.

....problem. Rigid docking is a particular case of the general flexible docking problem, where a rigid ligand ( key ) is docked onto a rigid protein receptor ( lock ) Heuristic rigid body methods have been developed (see for example [Katchalski Katzir et al. 1992, Jiang and Kim, 1991, Wang, 1991, Kuntz et al. 1982, Fischer et al. 1995] Yet, these methods do not take into account the conformational transitions that molecules may undergo. This shortcoming is exemplified by a database search for inhibitors to the HIV 1 protease [DesJarlais et al. 1990] which enables the prediction of only rigid docked ....

....1995] which allows partial flexibility in hydrogen bonding groups. None of these techniques enable hinge induced domain within receptors, although theoretically it seems feasible. Both DesJarlais et al. and Leach Kuntz [DesJarlais et al. 1986, Leach and Kuntz, 1992] use the DOCK based approach [Kuntz et al. 1982] for docking a flexible ligand onto a rigid receptor. The ligand is represented as a composition of its rigid parts. Each part is matched separately within the docking site. DesJarlais et al. DesJarlais et al. 1986] do not assume dependency on the order in which the ligand s parts are being ....

[Article contains additional citation context not shown here]

Kuntz, I., Blaney, J., Oatley, S., Langridge, R., and Ferrin, T. (1982). A geometric approach to macromolecule-ligand interactions. J. Mol. Biol., 161:269--288.

....bind to its ligand; either permanently, e.g. during transportation or inhibition, or temporarily e.g. in catalysis. One of the current challenges in computational biology is to predict reliably whether and how a pair of proteins might associate. This is often referred to as the docking problem [1, 2]. Several crystallographic structures of protein complexes have now been determined and these frequently exhibit high degrees of steric and chemical complementarity at the protein protein interface [3, 4, 5, 6, 7, 8] Often, docking algorithms are developed and re ned according to their ability to ....

....methods to test hundreds of thousands [15, 16] or many millions [17, 18] of distinct rigid body relative orientations. The most common way to reduce the amount of computation is to perform an initial geometric analysis of each surface to locate signi cant geometric features such as cavities [2], local knobs and holes [19] and their associated surface normals [16] These approaches reduce the complexity of the problem to a combinatorial search over a relatively small number of complementary surface features, which can be performed quite quickly using e.g. geometric hashing [15, 20] ....

I. D. Kuntz, J. M. Blaney, S. J. Oatley, R. Langridge, and T. E. Ferrin. A geometric approach to macromolecule-ligand interactions. J. Mol. Biol., 161(2):269-288, 1982.

....minimization (references 1 6 of [KSEF] were only partially successful. Geometric approaches (references 7 16 of [KSEF] including [Co] were much more successful, but (at least the earlier ones) were not reliable enough, and suffered from inacceptably long computation time [KSEF] see also [KBOL, JK]. The problem of detecting structural motifs in proteins was traditionally tackled by string matching techniques, applied to the primary structures of the proteins [SK] Other, more enhanced methods [RK, AM1, MARW] searched for the existence of predefined motifs in the secondary protein ....

I.D. Kuntz, J.M. Blaney, S.J. Oatley, R. Langridge, and T.E. Ferrin, A geometric approach to macromolecule-ligand interactions, J. Molecular Biology, 161 (1982) 269--288.

....against a single target protein, after obtaining the structure of this protein experimentally. This makes Autodock an important computational tool in the initial stages of drug design. 1.2 Prior Work Molecular docking has received much attention in computational biology. The DOCK program [8] was one of the first approaches to this problem, and current versions of it are still used. It attempts to find binding sites based on physical properties of the docking molecules, without doing a complete heuristic search of possible docked configurations. More recent efforts often employ an ....

Kuntz, I.D., Blaney, J.M., Oatley, S.J., Langridge, R., and Ferrin, T.E. (1982). "A Geometric Approach to Macromolecule-Ligand Interactions." Journal of Molecular Biology 161:269-288.

....The fundamental feature of the peptide docking problem is the development of accurate scoring functions. Many methods have relied on qualitative modeling of the peptide docking interactions. In the case of a rigid binding approximation, the use of shape complementarity has had some limited success [20]. These algorithms model the ligand and macromolecule according to their surface topology, and attempt to identify which complexes exhibit the best fit . Here scoring functions are based on the complementarity of the molecules, which, in most cases, is related to their solvent accessible surface ....

I. D. Kuntz, J. M. Blaney, S. J. Oatley, R. Landgridge and T. E. Ferrin, A geometric approach to macromolecule-ligand interactions, J. Mol. Biol., 161, (1982), 269-288.

....into planar slices and com plementarity of the molecular interfaces is studied amongst the digital contours formed by the intersection of the molecular surface with each gridded plane. There also has been some other interesting geometrybased work on drug design and protein substrate docking [12, 13, 15]. To the best of our knowledge, no prior work has been done in analytically defining the geometric interface of molecules based upon the concept of power diagrams. 3 Our approach Let the complete molecular surfaces defined for a probe radius ff for the molecules A and B be represented by S(A; ff) ....

Irwin D. Kuntz, Jeffrey M. Blaney, Stuart J. Oatley, Robert Langridge, and Thomas E. Ferrin. A geometric approach to macromolecule--ligand interactions. JMB, 161:269--288, 1982.

....which ligand atoms may be placed. The set of site points constitutes a negative image of the active regions of the receptor surface. Recently, Lin et al. 1994) proposed a representation which supplements such point information with surface normals for better discrimination. In another approach ((Kuntz et al. 1982), Shoichet Kuntz 1991) the features used are spheres. This algorithm generates one set of spheres which fill the ridges on the surface of the ligand and another set which fill the grooves on the receptor surface. That is, ligand spheres lie on the inside of the ligand, while the ....

....to searching for maximal cliques in this graph. Although clique finding is known to be an NP hard problem (Garey Johnson 1979) the authors argue that their approach is efficient in practice due to the geometric nature of the constraints imposed by the distances. The DOCK algorithm described in (Kuntz et al. 1982) also tries to maximize the number of features matched, although it does not guarantee the global maximum. The algorithm is as follows: first, systematically pair each ligand sphere with each receptor sphere. For each such pairing, choose a second pair which maximizes the number of further matches ....

[Article contains additional citation context not shown here]

Kuntz, I. D.; Blaney, J. M.; Oatley, S. J.; Langridge, R.; and Ferrin, T. E. 1982. A geometric approach to macromolecule--ligand interactions. Journal of Molecular Biology 161:269--288.

....contact between two molecular surfaces and there are no overlapping regions. This is a continuous problem. In order to solve this problem, we have to check all possible rigid transformations and find the best configuration that corresponds to the minimum interaction energy state. Kuntz et al. KBO82] generate a set of spheres that fill all pockets and grooves on the surface of the receptor molecule. The ligand molecule is represented by a set of spheres that approximately fill the space occupied by the ligand. A ligand sphere can be paired with a receptor sphere if each sphere belongs to a ....

I. Kuntz, J. Blaney, and S. Oatley. A geometric approach to macromolecule-ligand interactions. Journal of Molecular Biology, 1982.

....of accurate scoring functions. Due to the computational complexity of rigorous energy calculations, many methods have relied on qualitative modeling of the peptide docking interactions. In the case of a rigid binding approximation, the use of shape complementarity has had some limited success [93]. These algorithms model the ligand and macromolecule according to their surface topology, and attempt to identify which complexes exhibit the best fit . Here scoring functions are based on the complementarity of the molecules, which, in most cases, is related to their solvent accessible surface ....

....ligand proteins into one of matching similar shapes for these two molecules. This is accomplished by characterizing the binding site by a collection of spheres that lie on the outside of the receptor surface, and the ligand by a collection of spheres that lie on the inside of the ligand surface [39, 40, 93]. Potential matches are identified by grouping and comparing distances between the center of spheres for each molecule. Local refinement of translation and rotation vectors is used for the highest ranking matches. The complexity of the problem is, to some degree, obscured because it also depends ....

I. D. Kuntz, J. M. Blaney, S. J. Oatley, R. Landgridge and T. E. Ferrin, A geometric approach to macromolecule-ligand interactions, J. Mol. Biol., 161, (1982), 269-288.

....against a single target protein, after obtaining the structure of this protein experimentally. This makes Autodock an important computational tool in the initial stages of drug design. 2.2 Prior Work Molecular docking has received much attention in computational biology. The DOCK program [6] was one of the first approaches to this problem, and current versions of it are still used. It attempts to find binding sites based on physical properties of the docking molecules, without doing a complete heuristic search of possible docked configurations. More recent efforts often employ an ....

Kuntz, I.D., Blaney, J.M., Oatley, S.J., Langridge, R., and Ferrin, T.E. (1982). "A Geometric Approach to Macromolecule-Ligand Interactions." Journal of Molecular Biology 161:269-288.

No context found.

Kuntz I, Blaney J, Oatley S, Langridge R. Ferrin T. A geometric approach to macromolecule-ligand interactions. Journal of Molecular Biology 1982; 161:269--288.

No context found.

Kuntz I.D., Blaney J.M., Oatley S.J., Langridge R., Ferrin T.E. (1982) A Geometric Approach to Macromolecule-Ligand Interactions, J. Mol. Biol., 161, 269-288.

No context found.

Kuntz, I.D., Blaney, J.M., Oatley, S.J., Langridge, R., Ferrin, T.E. A geometric approach to macromolecule-ligand interactions. J. Mol. Biol. 161:269--288, 1982.

No context found.

Kuntz I, Blaney J, Oatley S, Langridge R, Ferrin T. A geometric approach to macromolecule-ligand interactions. J Mol Biol 1982; 161:269--288.

No context found.

Kuntz, I., Blaney, J., Oatley, S., Langridge, R., and Ferrin, T. A geometric approach to macromolecule-ligand interactions. J. Mol. Biol., 161:269--288, 1982.

No context found.

I.D. Kuntz, J.M. Blaney, S.J. Oatley, R. Langridge and T.E. Ferrin: "A Geometric Approach to Macromolecule-Ligand Interactions." J. Mol. Biol., vol. 161, 1982, pp. 269-- 288.

No context found.

I.D. Kuntz, J.M. Blaney, S.J. Oatley, R. Langridge and T.E. Ferrin: "A Geometric Approach to Macromolecule-Ligand Interactions." J. Mol. Biol., vol. 161, 1982, pp. 269--288.

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