Roland A. Pache

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Genome sequencing projects provide nearly complete lists of the individual components present in an organism, but reveal little about how they work together. Follow-up initiatives have deciphered thousands of dynamic and context-dependent interrelationships between gene products that need to be analyzed with novel bioinformatics approaches able to capture(More)
Virtually every process in a cell is carried out by macromolecular complexes whose actions need to be perfectly orchestrated. The synchronization and regulation of these biological functions is indeed critical and is usually carried out by complex networks of transient protein interactions. Here, we review some of the many strategies that proteins in(More)
Accurate energy functions are critical to macromolecular modeling and design. We describe new tools for identifying inaccuracies in energy functions and guiding their improvement, and illustrate the application of these tools to the improvement of the Rosetta energy function. The feature analysis tool identifies discrepancies between structures deposited in(More)
The many ongoing genome sequencing initiatives are delivering comprehensive lists of the individual molecular components present in an organism, but these reveal little about how they work together. Follow-up initiatives are revealing thousands of interrelationships between gene products that need to be analyzed with novel bioinformatics approaches able to(More)
Understanding how individual genes contribute towards the fitness of an organism is a fundamental problem in biology. Although recent genome-wide screens have generated abundant data on quantitative fitness for single gene knockouts, very few studies have systematically integrated other types of biological information to understand how and why deletion of(More)
Aurora A is a serine/threonine kinase that is essential for a wide variety of cell-cycle-related events, but only a small number of its substrates are known. We present and validate a strategy by which to identify Aurora A substrates and their phosphorylation sites. We developed a computational approach integrating various types of biological information to(More)
Structurally disordered regions play a key role in protein-protein interaction networks and the evolution of highly connected proteins, enabling the molecular mechanisms for multiple binding. However, the role of protein disorder in the evolution of interaction networks has only been investigated through the analysis of individual proteins, making it(More)
The dominant conceptual reductionism in drug discovery has resulted in many promising drug candidates to fail during the last clinical phases, mainly due to a lack of knowledge about the patho-physiological pathways they are acting on. Consequently, to increase the revenues of the drug discovery process, we need to improve our understanding of the molecular(More)
The development and validation of computational macromolecular modeling and design methods depend on suitable benchmark datasets and informative metrics for comparing protocols. In addition, if a method is intended to be adopted broadly in diverse biological applications, there needs to be information on appropriate parameters for each protocol, as well as(More)
For high-throughput structural studies of protein complexes of composition inferred from proteomics data, it is crucial that candidate complexes are selected accurately. Herein, we exemplify a procedure that combines a bioinformatics tool for complex selection with in vivo validation, to deliver structural results in a medium-throughout manner. We have(More)