On NP-Hardness of the Paired de Bruijn Sound Cycle Problem

The paired de Bruijn graph is an extension of de Bruijn graph incorporating mate pair information for genome assembly proposed by Mevdedev et al. However, unlike in an ordinary de Bruijn graph, not every path or cycle in a paired de Bruijn graph will spell a string, because there is an additional soundness constraint on the path. In this paper we show that the problem of checking if there is a sound cycle in a paired de Bruijn graph is NP-hard in general case. We also explore some of its special cases, as well as a modified version where the cycle must also pass through every edge.Comment: Peer-reviewed and presented as part of the 13th Workshop on Algorithms in Bioinformatics (WABI2013

Betulin-related esters from birch bark tar: identification, origin and archaeological significance

International audienc

Nonlinear evolution of two fast-particle-driven modes near the linear stability threshold

A system of two coupled integro-differential equations is derived and solved for the non-linear evolution of two waves excited by the resonant interaction with fast ions just above the linear instability threshold. The effects of a resonant particle source and classical relaxation processes represented by the Krook, diffusion, and dynamical friction collision operators are included in the model, which exhibits different nonlinear evolution regimes, mainly depending on the type of relaxation process that restores the unstable distribution function of fast ions. When the Krook collisions or diffusion dominate, the wave amplitude evolution is characterized by modulation and saturation. However, when the dynamical friction dominates, the wave amplitude is in the explosive regime. In addition, it is found that the finite separation in the phase velocities of the two modes weakens the interaction strength between the modes

Betulin-related esters from birch bark tar: Identification, origin and archaeological significance

Birch bark tar, an organic material frequently encountered during archaeological excavations, has been identified from its lipid composition on the cracks of a ceramic dated to the late Neolithic. Lipids of this black substance were dominated by a characteristic triterpenoid assemblage of lupane-related triterpenoids from birch bark together with their thermal degradation products formed during preparation of the tar. Among the latter, four main series of unusual triterpenoid esters have been detected and were postulated to correspond to esters of Delta2-betulin and Delta2-dihydrobetulin based on their mass spectra and hydrolysis experiments. Their conclusive identification has been achieved by synthesis of reference compounds. These compounds most likely originate from the esterification between triterpenoid alcohols related to betulin and fatty acids from suberin formed upon heating of birch bark tar. They could be considered as markers of intense heating during birch bark tar preparation using the “single pot“ procedure

A theoretical study of the stability of disulfide bridges in various β-sheet structures of protein segment models

Electron structure calculations are used to explore stabilization effects of disulfide bridges in a (Ala–Cys–Ala–Cys–Ala)2 β-sheet model both in the parallel and the anti-parallel (103142 and 143102) arrangements. Stabilities were calculated using a redox reaction involving a weak oxidizing agent (1,4-benzoquinone). The results show that both inter- and intra-strand disulfide SS-bridges stabilize the β-sheet backbone fold. However, inter-strand SS-bridges give more stability than their intra-strand counterparts. For both single and double disulfide linked conformations, stabilization was larger for the parallel than for the anti-parallel β-sheet arrangements

SPR-measured dissociation kinetics of PROTAC ternary complexes influence target degradation rate

Bifunctional degrader molecules, known as proteolysis-targeting chimeras (PROTACs), function by recruiting a target to an E3 ligase, forming a target/PROTAC/ligase ternary complex. Despite the importance of this key intermediate species, no detailed validation of a method to directly determine binding parameters for ternary complex kinetics has been reported, and it remains to be addressed whether tuning the kinetics of PROTAC ternary complexes may be an effective strategy to improve the efficiency of targeted protein degradation. Here, we develop an SPR-based assay to quantify the stability of PROTAC-induced ternary complexes by measuring for the first time the kinetics of their formation and dissociation <i>in vitro</i> using purified proteins. We benchmark our assay using four PROTACs that target the bromodomains (BDs) of bromodomain and extraterminal domain proteins Brd2, Brd3, and Brd4 to the von Hippel–Lindau E3 ligase (VHL). We reveal marked differences in ternary complex off-rates for different PROTACs that exhibit either positive or negative cooperativity for ternary complex formation relative to binary binding. The positively cooperative degrader MZ1 forms comparatively stable and long-lived ternary complexes with either Brd4^BD2 or Brd2^BD2 and VHL. Equivalent complexes with Brd3^BD2 are destabilized due to a single amino acid difference (Glu/Gly swap) present in the bromodomain. We observe that this difference in ternary complex dissociative half-life correlates to a greater initial rate of intracellular degradation of Brd2 and Brd4 relative to Brd3. These findings establish a novel assay to measure the kinetics of PROTAC ternary complexes and elucidate the important kinetic parameters that drive effective target degradation