A global optimization algorithm for protein surface alignment

Background A relevant problem in drug design is the comparison and recognition of protein binding sites. Binding sites recognition is generally based on geometry often combined with physico-chemical properties of the site since the conformation, size and chemical composition of the protein surface are all relevant for the interaction with a specific ligand. Several matching strategies have been designed for the recognition of protein-ligand binding sites and of protein-protein interfaces but the problem cannot be considered solved. Results In this paper we propose a new method for local structural alignment of protein surfaces based on continuous global optimization techniques. Given the three-dimensional structures of two proteins, the method finds the isometric transformation (rotation plus translation) that best superimposes active regions of two structures. We draw our inspiration from the well-known Iterative Closest Point (ICP) method for three-dimensional (3D) shapes registration. Our main contribution is in the adoption of a controlled random search as a more efficient global optimization approach along with a new dissimilarity measure. The reported computational experience and comparison show viability of the proposed approach. Conclusions Our method performs well to detect similarity in binding sites when this in fact exists. In the future we plan to do a more comprehensive evaluation of the method by considering large datasets of non-redundant proteins and applying a clustering technique to the results of all comparisons to classify binding sites

An interior point method for nonlinear constrained derivative-free optimization

In this paper we consider constrained optimization problems where both the objective and constraint functions are of the black-box type. Furthermore, we assume that the nonlinear inequality constraints are non-relaxable, i.e. their values and that of the objective function cannot be computed outside of the feasible region. This situation happens frequently in practice especially in the black-box setting where function values are typically computed by means of complex simulation programs which may fail to execute if the considered point is outside of the feasible region. For such problems, we propose a new derivative-free optimization method which is based on the use of a merit function that handles inequality constraints by means of a log-barrier approach and equality constraints by means of a quadratic penalty approach. We prove convergence of the proposed method to KKT stationary points of the problem under quite mild assumptions. Furthermore, we also carry out a preliminary numerical experience on standard test problems and comparison with a state-of-the-art solver which shows efficiency of the proposed method.Comment: We dropped the convexity assumption to take into account that convexity is no longer required, we changed the theoretical analysis, exposition of the main algorithm has changed. We first present a simpler method and then the main algorithm. Numerical results have been a lot extended by adding some compariso

A clustering heuristic to improve a derivative-free algorithm for nonsmooth optimization

In this paper we propose an heuristic to improve the performances of the recently proposed derivative-free method for nonsmooth optimization CS-DFN. The heuristic is based on a clustering-type technique to compute an estimate of Clarke’s generalized gradient of the objective function, obtained via calculation of the (approximate) directional derivative along a certain set of directions. A search direction is then calculated by applying a nonsmooth Newton-type approach. As such, this direction (as it is shown by the numerical experiments) is a good descent direction for the objective function. We report some numerical results and comparison with the original CS-DFN method to show the utility of the proposed improvement on a set of well-known test problems

Derivative-free methods for mixed-integer nonsmooth constrained optimization

In this paper, we consider mixed-integer nonsmooth constrained optimization problems whose objective/constraint functions are available only as the output of a black-box zeroth-order oracle (i.e., an oracle that does not provide derivative information) and we propose a new derivative-free linesearch-based algorithmic framework to suitably handle those problems. We first describe a scheme for bound constrained problems that combines a dense sequence of directions (to handle the nonsmoothness of the objective function) with primitive directions (to handle discrete variables). Then, we embed an exact penalty approach in the scheme to suitably manage nonlinear (possibly nonsmooth) constraints. We analyze the global convergence properties of the proposed algorithms toward stationary points and we report the results of an extensive numerical experience on a set of mixed-integer test problems

Improving P300 Speller performance by means of optimization and machine learning

Brain-Computer Interfaces (BCIs) are systems allowing people to interact with the environment bypassing the natural neuromuscular and hormonal outputs of the peripheral nervous system (PNS). These interfaces record a user's brain activity and translate it into control commands for external devices, thus providing the PNS with additional artificial outputs. In this framework, the BCIs based on the P300 Event-Related Potentials (ERP), which represent the electrical responses recorded from the brain after specific events or stimuli, have proven to be particularly successful and robust. The presence or the absence of a P300 evoked potential within the EEG features is determined through a classification algorithm. Linear classifiers such as SWLDA and SVM are the most used for ERPs' classification. Due to the low signal-to-noise ratio of the EEG signals, multiple stimulation sequences (a.k.a. iterations) are carried out and then averaged before the signals being classified. However, while augmenting the number of iterations improves the Signal-to-Noise Ratio (SNR), it also slows down the process. In the early studies, the number of iterations was fixed (no stopping), but recently, several early stopping strategies have been proposed in the literature to dynamically interrupt the stimulation sequence when a certain criterion is met to enhance the communication rate. In this work, we explore how to improve the classification performances in P300 based BCIs by combining optimization and machine learning. First, we propose a new decision function that aims at improving classification performances in terms of accuracy and Information Transfer Rate both in a no stopping and early stopping environment. Then, we propose a new SVM training problem that aims to facilitate the target-detection process. Our approach proves to be effective on several publicly available datasets.Comment: 32 pages, research articl

Derivative-free global design optimization in ship hydrodynamics by local hybridization

A derivative-free global design optimization of the DTMB 5415 model is presented, using local hybridizations of two global algorithms, DIRECT (DIviding RECTangles) and PSO (Particle Swarm Optimization). The optimization aims at the reduction of the calm-water resistance at Fr = 0.25, using six design variables modifying hull and sonar dome. Simulations are conducted using potential flow with a friction model. Hybrid algorithms show a faster convergence towards the global minimum than the original global methods and are a viable option for design optimization, especially when computationally expensive objective functions are involved. A resistance reduction of 16% was achieved

Unit Commitment by Nonlinear Mixed Variable Programming

In this paper we consider the unit commitment problem and its solution via a nonlinear mixed variable programming algorithm. Indeed, the natural formulation of the problem involves both integer and continuous variables thus yielding an optimization problem solvable by a mixed variable algorithm. Our formulation of the problem besides taking into account ramp rate and minimum up and down time constraints, handles the size of the operator and the uncertainty related to the selling prices by defining dierent residual demand curves and using a scenario formulation. The objective function is indeed given by the expected value of the revenue over the dierent scenarios minus a term which takes into account the risk related to the decision. We report results for an operator managing a single unit and three units at the same tim

A DERIVATIVE-FREE ALGORITHM FOR INEQUALITY CONSTRAINED NONLINEAR PROGRAMMING VIA SMOOTHING OF AN l(infinity) PENALTY FUNCTION

In this paper we consider inequality constrained nonlinear optimization problems where the first order derivatives of the objective function and the constraints cannot be used. Our starting point is the possibility to transform the original constrained problem into an unconstrained or linearly constrained minimization of a nonsmooth exact penalty function. This approach shows two main difficulties: the first one is the nonsmoothness of this class of exact penalty functions which may cause derivative-free codes to converge to nonstationary points of the problem; the second one is the fact that the equivalence between stationary points of the constrained problem and those of the exact penalty function can only be stated when the penalty parameter is smaller than a threshold value which is not known a priori. In this paper we propose a derivative-free algorithm which overcomes the preceding difficulties and produces a sequence of points that admits a subsequence converging to a Karush-Kuhn-Tucker point of the constrained problem. In particular the proposed algorithm is based on a smoothing of the nondifferentiable exact penalty function and includes an updating rule which, after at most a finite number of updates, is able to determine a "right value" for the penalty parameter. Furthermore we present the results obtained on a real world problem concerning the estimation of parameters in an insulin-glucose model of the human body