Knowledge-based energy functions for computational studies of proteins

This chapter discusses theoretical framework and methods for developing knowledge-based potential functions essential for protein structure prediction, protein-protein interaction, and protein sequence design. We discuss in some details about the Miyazawa-Jernigan contact statistical potential, distance-dependent statistical potentials, as well as geometric statistical potentials. We also describe a geometric model for developing both linear and non-linear potential functions by optimization. Applications of knowledge-based potential functions in protein-decoy discrimination, in protein-protein interactions, and in protein design are then described. Several issues of knowledge-based potential functions are finally discussed.Comment: 57 pages, 6 figures. To be published in a book by Springe

Efficient Reconstruction of Metabolic Pathways by Bidirectional Chemical Search

One of the main challenges in systems biology is the establishment of the metabolome: a catalogue of the metabolites and biochemical reactions present in a specific organism. Current knowledge of biochemical pathways as stored in public databases such as KEGG, is based on carefully curated genomic evidence for the presence of specific metabolites and enzymes that activate particular biochemical reactions. In this paper, we present an efficient method to build a substantial portion of the artificial chemistry defined by the metabolites and biochemical reactions in a given metabolic pathway, which is based on bidirectional chemical search. Computational results on the pathways stored in KEGG reveal novel biochemical pathways

Cp(graph): Introducing a graph computation domain in constraint programming

Abstract. In an increasing number of domains such as bioinformatics, combinatorial graph problems arise. We propose a novel way to solve these problems, mainly those that can be translated to constrained subgraph finding. Our approach extends constraint programming by introducing CP(Graph), a new computation domain focused on graphs including a new type of variable: graph domain variables as well as constraints over these variables and their propagators. These constraints are subdivided into kernel constraints and additional constraints formulated as networks of kernel constraints. For some of these constraints a dedicated global constraint and its associated propagator are sketched. CP(Graph) is integrated with finite domain and finite sets computation domains, allowing the combining of constraints of these domains with graph constraints. A prototype of CP(Graph) built over finite domains and finite sets in Oz is presented. And we show that a problem of biochemical network analysis can be very simply described and solved within CP(Graph).