Docking by Monte Carlo minimization with a solvation correction: Application to an FKBP - substrate complex
A Monte Carlo docking procedure that combines random displacements of the substrate and protein side chains with minimization of the enzyme]substrate complex is described and applied to finding the binding mode of the blocked tetrapeptide N-acetyl-Leu-Pro-Phe-methylamide to the FK506 binding protein Ž .  The tetrapeptide, an analog of the preferred FKBP substrate, and the FKBP binding site are flexible during the docking procedure. The twisted-imide transition-state form of the substrate is used during docking. The enzyme charges are scaled individually to account for solvent screening of specific binding site residues during the Monte Carlo sampling. To evaluate the relative binding free energies of the resulting structures, a rapid method for calculating polar and nonpolar solvation effects is introduced. Accurate electrostatic solute]solvent energies are calculated by solving the finite-difference linearized Poisson]Boltzmann equation; nonpolar contributions to the stability of the different conformers are estimated by the free energy of cavity formation, which is obtained from the molecular surface, and the solute]solvent van der Waals energy, which is calculated with a continuum approach. In the conformation of the enzyme]substrate complex with the lowest free energy, the tetrapeptide is bound as a type VIa proline turn with solvent accessible ends to permit longer polypeptide chains to act as substrates. Except for the imide carbonyl, which is involved in polar interactions with aromatic side chains of the FKBP binding *Present address: Pharmaceutical Research, F. Hoffmann]La Roche Ltd., CH-4070 Basel, Switzerland. Author to whom all correspondence should be addressed. ( 21 CAFLISCH, FISCHER, AND KARPLUS site, all of the seven potential hydrogen bond donors or acceptors of the tetrapeptide are satisfied. The FKBP binding site has a similar conformation in the substrate complex as in the FKBP-FK506 cocrystal structure, except for the predicted reorientation of the Tyr 82 hydroxyl, which plays an important role in substrate binding. The present model for the FKBP]substrate complex is in agreement with the recently determined crystal structure of a cyclic peptide]FK506 hybrid bound to FKBP and supports the structure obtained previously by iterative model building. In addition, it is consistent with the observed effects of FKBP point mutations on the enzyme activity. The approach described here should be useful, in general, for the prediction of the structure of a molecule in solution or as part of a complex. It provides for the effective sampling of conformational space and for the inclusion of solvent effects. Q 1997 by John Wiley & Sons, Inc.

title: How well does charge reparametrisation account for solvent screening in molecular mechanics calculations? The example of myosin
abstract: The rate constant of an enzyme-catalysed reaction is one of the major target properties to understand protein function. Atomic-detail computer simulations can in principle be used to estimate rate constants from the energy profile along the reaction coordinate. For such simulations, molecular mechanics is combined with a quantum description of the reaction process. In molecular mechanics calculations, the electrostatic field is represented by the Coulomb potential of partial atomic charges which have been parametrised for small building blocks in vacuum and transferred to the macromolecule. In aqueous solution, however, the electrostatic interactions are affected by the solvent polarization. While this can be described by numerically solving the Poisson-Boltzmann equation, it is computationally expensive. A simple approximation to this is to optimally reproduce the electrostatic potential in solution by reparametrising the partial atomic charges in such a way that a simple Coulomb potential can still be used. Such a procedure would allow to perform fast calculations of reaction processes in proteins while accounting for the solvent screening effect. Here, this method is tested on myosin, a motor protein that is both an enzyme and exists in very different conformations.

title: Chosen IV Statistical Analysis for Key Recovery Attacks on Stream Ciphers
abstract: A recent framework for chosen IV statistical distinguishing analysis of stream ciphers is exploited and formalized to provide new methods for key recovery attacks. As an application, a key recovery attack on simplified versions of two eSTREAM Phase 3 candidates is given: For Grain-128 with IV initialization reduced to up to 180 of its 256 iterations, and for Trivium with IV initialization reduced to up to 672 of its 1152 iterations, it is experimentally demonstrated how to deduce a few key bits. Evidence is given that the present analysis is not applicable on Grain-128 or Trivium with full IV initialization.

title: Automatic Identification of Diatoms Using Visual Human-Interpretable Features
abstract: In this paper we present an identification scheme for diatoms using visual human-interpretable features. Diatoms are unicellular algae found in water and other places wherever there is humidity and enough light for photosynthesis. The automatic identification of diatoms has applications in a number of areas, for example, environmental monitoring and climate research. The overall identification is performed by an ensemble of multiple decision trees following the bagging approach. The use of human-interpretable features in contrast to traditional features, such as Fourier descriptors or moment invariants, makes it possible for a human expert to verify the induced decision trees and opens up the possibility of integrating human expert knowledge into automatically derived decision trees.

title: Non-randomness in eSTREAM Candidates Salsa20 and TSC-4
abstract: Stream cipher initialisation should ensure that the initial state or keystream is not detectably related to the key and initialisation vector. In this paper we analyse the key/IV setup of the eSTREAM Phase 2 candidates Salsa20 and TSC-4. In the case of Salsa20 we demonstrate a key recovery attack on six rounds and observe non-randomness after seven. For TSC-4, non-randomness over the full eight-round initialisation phase is detected, but would also persist for more rounds.

title: Face authentication with Gabor information on deformable graphs
abstract: Elastic graph matching has been proposed as a practical implementation of dynamic link matching, which is a neural network with dynamically evolving links between a reference model and an input image. Each node of the graph contains features that characterize the neighborhood of its location in the image. The elastic graph matching usually consists of two consecutive steps, namely a matching with a rigid grid, followed by a deformation of the grid, which is actually the elastic part. The deformation step is introduced in order to allow for some deformation, rotation, and scaling of the object to be matched. This method is applied here to the authentication of human faces where candidates claim an identity that is to be checked. The matching error as originally suggested is not powerful enough to provide satisfying results in this case. We introduce an automatic weighting of the nodes according to their significance. We also explore the significance of the elastic deformation for an application of face-based person authentication. We compare performance results obtained with and without the second matching step. Results show that the deformation step slightly increases the performance, but has lower influence than the weighting of the nodes. The best results are obtained with the combination of both aspects. The results provided by the proposed method compare favorably with two methods that require a prior geometric face normalization, namely the synergetic and eigenface approaches.

title: Fusion of audio and video information for multi modal person authentication
abstract: We present an algorithm functioning as a supervisor module in a multi-expert decision making machine. It uses the Bayes theory in order to estimate the biases of individual expert opinions. The biases are used to calibrate and conciliate expert opinions to a single decision. This supervision technique is applied to the real case of a person authentication technique using two modalities, face and speech. The visual part involves the matching of a coarse grid containing Gabor phase information from face images. The acoustic part is performed by a text-dependent speaker verification system based on Hidden Markov Models. Experimental results show that the proposed fusion method improves the quality of individual expert decisions by reaching success rates of 99.5%.