Frustration in Biomolecules

Biomolecules are the prime information processing elements of living matter. Most of these inanimate systems are polymers that compute their structures and dynamics using as input seemingly random character strings of their sequence, following which they coalesce and perform integrated cellular functions. In large computational systems with a finite interaction-codes, the appearance of conflicting goals is inevitable. Simple conflicting forces can lead to quite complex structures and behaviors, leading to the concept of "frustration" in condensed matter. We present here some basic ideas about frustration in biomolecules and how the frustration concept leads to a better appreciation of many aspects of the architecture of biomolecules, and how structure connects to function. These ideas are simultaneously both seductively simple and perilously subtle to grasp completely. The energy landscape theory of protein folding provides a framework for quantifying frustration in large systems and has been implemented at many levels of description. We first review the notion of frustration from the areas of abstract logic and its uses in simple condensed matter systems. We discuss then how the frustration concept applies specifically to heteropolymers, testing folding landscape theory in computer simulations of protein models and in experimentally accessible systems. Studying the aspects of frustration averaged over many proteins provides ways to infer energy functions useful for reliable structure prediction. We discuss how frustration affects folding, how a large part of the biological functions of proteins are related to subtle local frustration effects and how frustration influences the appearance of metastable states, the nature of binding processes, catalysis and allosteric transitions. We hope to illustrate how Frustration is a fundamental concept in relating function to structural biology.Comment: 97 pages, 30 figure

Optimal modeling for complex system design

The article begins with a brief introduction to the theory describing optimal data compression systems and their performance. A brief outline is then given of a representative algorithm that employs these lessons for optimal data compression system design. The implications of rate-distortion theory for practical data compression system design is then described, followed by a description of the tensions between theoretical optimality and system practicality and a discussion of common tools used in current algorithms to resolve these tensions. Next, the generalization of rate-distortion principles to the design of optimal collections of models is presented. The discussion focuses initially on data compression systems, but later widens to describe how rate-distortion theory principles generalize to model design for a wide variety of modeling applications. The article ends with a discussion of the performance benefits to be achieved using the multiple-model design algorithms

2D Iterative MAP Detection: Principles and Applications in Image Restoration

The paper provides a theoretical framework for the two-dimensional iterative maximum a posteriori detection. This generalization is based on the concept of detection algorithms BCJR and SOVA, i.e., the classical (one-dimensional) iterative detectors used in telecommunication applications. We generalize the one-dimensional detection problem considering the spatial ISI kernel as a two-dimensional finite state machine (2D FSM) representing a network of the spatially concatenated elements. The cellular structure topology defines the design of the 2D Iterative decoding network, where each cell is a general combination-marginalization statistical element (SISO module) exchanging discrete probability density functions (information metrics) with neighboring cells. In this paper, we statistically analyse the performance of various topologies with respect to their application in the field of image restoration. The iterative detection algorithm was applied on the task of binarization of images taken from a CCD camera. The reconstruction includes suppression of the defocus caused by the lens, CCD sensor noise suppression and interpolation (demosaicing). The simulations prove that the algorithm provides satisfactory results even in the case of an input image that is under-sampled due to the Bayer mask

Spectral Sequence Motif Discovery

Sequence discovery tools play a central role in several fields of computational biology. In the framework of Transcription Factor binding studies, motif finding algorithms of increasingly high performance are required to process the big datasets produced by new high-throughput sequencing technologies. Most existing algorithms are computationally demanding and often cannot support the large size of new experimental data. We present a new motif discovery algorithm that is built on a recent machine learning technique, referred to as Method of Moments. Based on spectral decompositions, this method is robust under model misspecification and is not prone to locally optimal solutions. We obtain an algorithm that is extremely fast and designed for the analysis of big sequencing data. In a few minutes, we can process datasets of hundreds of thousand sequences and extract motif profiles that match those computed by various state-of-the-art algorithms.Comment: 20 pages, 3 figures, 1 tabl