otease-protein inhibitor and four antibody-antigen complexes. A large number of putative docked complexes have already been generated for the test systems using our rigid-body docking program, FTDOCK. They include geometries that closely resemble the crystal complex, and therefore act as a test for the renement procedure. In the protease-inhibitors, geometries that resemble the crystal complex are ranked in the top four solutions for four out of ve systems when solvation is included in the energy function, against a background of between 26 and 364 complexes in the data set. The results for the antibody-antigen complexes are not as encouraging, with only two of the four systems showing discrimination. It would appear that these results reect the somewhat different binding mechanism dominant in the two types of protein-protein complex. Binding in the protease-inhibitors appears to be "lock and key" in nature. The xed backbone and mobile side-chain representation provide a good model for

Abstract. We present a new algorithm for unbound (real life) docking of molecules, whether protein–protein or protein–drug. The algorithm carries out rigid docking, with surface variability/flexibility implicitly addressed through liberal intermolecular penetration. The high efficiency of the algorithm is the outcome of several factors: ( � ) focusing initial molecular surface fitting on localized, curvature based surface patches; (�� � ) use of Geometric Hashing and Pose Clustering for initial transformation detection; (���� � ) accurate computation of shape complementarity utilizing the Distance Transform; (�� � ) efficient steric clash detection and geometric fit scoring based on a multi-resolution shape representation; and ( �) utilization of biological information by focusing on hot spot rich surface patches. The algorithm has been implemented and applied to a large number of cases. 1

Here we carry out an examination of shape complementarity as a criterion in protein--protein docking and binding. Specifically, we examine the quality of shape complementarity as a critical determinant not only in the docking of 26 protein--protein "bound", complexed cases, but in particular, of 19 "unbound" protein--protein cases, where the structures have been determined separately. In all cases, entire molecular surfaces are utilized in the docking, with no consideration of the location of the active site, or of particular residues/atoms in either the receptor or the ligand which participate in the binding. To evaluate the goodness of the strictly geometry-based shape complementarity in the docking process as compared to the main favorable and unfavorable energy components, we study systematically a potential correlation between each of these components and the RMSD of the "unbound" protein--protein cases. Specifically, we examine the non-polar buried surface area, polar b...

In this work we present an algorithm developed to handle biomolecular structural recognition problems, as part of an interdisciplinary research endeavor of the Computer Vision and Molecular Biology fields. A key problem is rational drug design and in biomolecular structural recognition is the generation of binding modes between two molecules, also known as molecular docking. Geometrical fitness is a necessary condition for molecular interaction. Hence, docking a ligand (e.g., a drug molecule or a protein molecule), to a protein receptor (e.g., enzyme), involves recognition of molecular surfaces. Conformational transitions by `hinge-bending' involves rotational movements of relatively rigid parts with respect to each other. The generation of docked binding modes between two associating molecules depends on their three dimensional structures (3-D) and their conformational flexibility. In comparison to the particular case of rigid-body docking, the computational difficulty grows considera...

Here, we describe two freely available web servers for molecular docking. The PatchDock method performs structure prediction of protein–protein and protein– small molecule complexes. The SymmDock method predicts the structure of a homomultimer with cyclic symmetry given the structure of the monomeric unit. The inputs to the servers are either protein PDB codes or uploaded protein structures. The services are available at

In this paper we present a new technique for partial surface and volume matching of images in three dimensions. In this problem, we are given two objects in 3-space, each represented as a set of points, scattered uniformly along its boundary or inside its volume. The goal is to find a rigid motion of one object which makes a sufficiently large portion of its boundary lying sufficiently close to a corresponding portion of the boundary of the second object. This is an important problem in pattern recognition and in computer vision, with many industrial, medical, and chemical applications. Our algorithm is based on assigning a directed footprint to every point of the two sets, and locating all the pairs of points (one of each set) whose undirected components of the footprints are sufficiently similar. The algorithm then computes for each such pair of points all the rigid transformations that map the first point to the second, while making the respective direction components of ...

We propose a parallel hyzwC genetic algorithm for flexible protein-protein docking in order to improve the conventional "rigid-body models to manipulate protein-protein interactions. he proposed hyPKR algorithm is a combination of an evolutionary algorithm with a simulated annealing one,ye,TPKC a powerful protein-complex conformation-searching engine. Parallelization of the procedure makes possible to reach high algorithm performance, in both, execution times and size of treated monomers and complexes. Knowledge on side chain flexibility is extracted by means of an exhaustiveanalyPT ofcryPzKT"K[w[#Ty data on proteins and protein complexes. Results demonstrate the competency of the algorithm since comparison of calculated andcryRwwGT"KGC[#T data accounts for a maximum of 2.5 A in RMS difference, including side chain conformation. he syTP allows routine analyeT of this fundamental molecularbiology problem important to elucidate bio-macromolecular function in biophyophT and biochemical mechanisms involving molecular recognition and interaction,yeracti simultaneously clues for designing new proteins andenzyGz directed to different purposes.

Abstract. We give an algorithm that locally improves the fit between two proteins modeled as space-filling diagrams. The algorithm defines the fit in purely geometric terms and improves by applying a rigid motion to one of the two proteins. Our implementation of the algorithm takes between three and ten seconds and converges with high likelihood to the correct docked configuration, provided it starts at a position away from the correct one by at most 18 degrees of rota-tion and at most §© ¨ � ˚ of translation. The speed and convergence radius make this an attractive algorithm to use in combination with a coarse sampling of the six-dimensional space of rigid motions. 1

We have developed and implemented a parallel distributed algorithm for the rigid-body protein docking problem. The algorithm is based on a new fitness function for evaluating the surface matching of a given conformation. The fitness function is defined as the weighted sum of two contact measures the geometric contact measure and the chemical contact measure. The geometric contact measure measures the "size" of the contact area of two molecules. It is a potential function that counts the "van der Waals contacts" between the atoms of the two molecules (the algorithm does not compute the Lennard-Jones potential). The chemical contact measure is also based on the "van der Waals contacts" principle: We consider all atom pairs that have a "van der Waals" contact, but instead of adding a constant for each pair (a; b) we add a "chemical weight" that depends on the atom pair (a; b). We tested our docking algorithm with a test set that contains the test examples of Norel et al. [NLWN94] and Fisc...

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