Abstract
To date, more than 263 million people have been infected with SARS-CoV-2 during the COVID-19 pandemic. In many countries, the global spread occurred in multiple pandemic waves characterized ...by the emergence of new SARS-CoV-2 variants. Here we report a sequence and structural-bioinformatics analysis to estimate the effects of amino acid substitutions on the affinity of the SARS-CoV-2 spike receptor binding domain (RBD) to the human receptor hACE2. This is done through qualitative electrostatics and hydrophobicity analysis as well as molecular dynamics simulations used to develop a high-precision empirical scoring function (ESF) closely related to the linear interaction energy method and calibrated on a large set of experimental binding energies. For the latest variant of concern (VOC), B.1.1.529 Omicron, our Halo difference point cloud studies reveal the largest impact on the RBD binding interface compared to all other VOC. Moreover, according to our ESF model, Omicron achieves a much higher ACE2 binding affinity than the wild type and, in particular, the highest among all VOCs except Alpha and thus requires special attention and monitoring.
We present Ultimate TreeAutomizer, a solver for satisfiability of sets of constrained Horn clauses. Constrained Horn clauses (CHC) are a fragment of first order logic with attractive properties in ...terms of expressiveness and accessibility to algorithmic solving. Ultimate TreeAutomizer is based on the techniques of trace abstraction, tree automata and tree interpolation. This paper serves as a tool description for TreeAutomizer in CHC-COMP 2019.
The concentration of S-nitrosothiols (RSNOs), endogenous transporters of the signaling molecule nitric oxide (NO), fluctuate greatly in physiology often as a function of disease state. RSNOs may be ...measured indirectly by cleaving the S–N bond and monitoring the liberated NO. While ultraviolet photolysis and reductive-based cleavage both decompose RSNOs to NO, poor selectivity and the need for additional reagents preclude their utility clinically. Herein, we report the coupling of visible photolysis (i.e., 500–550 nm) and amperometric NO detection to quantify RSNOs with greater selectivity and sensitivity. Enhanced sensitivity (up to 1.56 nA μM–1) and lowered theoretical detection limits (down to 30 nM) were achieved for low molecular weight RSNOs (i.e., S-nitrosoglutathione, S-nitrosocysteine) by tuning the irradiation exposure. Detection of nitrosated proteins (i.e., S-nitrosoalbumin) was also possible, albeit at a decreased sensitivity (0.11 nA μM–1). This detection scheme was used to measure RSNOs in plasma and illustrate the potential of this method for future physiological studies.
EPTCS 296, 2019, pp. 42-47 We present Ultimate TreeAutomizer, a solver for satisfiability of sets of
constrained Horn clauses. Constrained Horn clauses (CHC) are a fragment of
first order logic with ...attractive properties in terms of expressiveness and
accessibility to algorithmic solving. Ultimate TreeAutomizer is based on the
techniques of trace abstraction, tree automata and tree interpolation. This
paper serves as a tool description for TreeAutomizer in CHC-COMP 2019.
In theorem prover or SMT solver based verification, the program to be verified is often given in an intermediate verification language such as Boogie, Why, or CHC. This setting raises new challenges. ...We investigate a preprocessing step which takes the similar role that alias analysis plays in verification, except that now, a (mathematical) map is used to model the memory or a data object of type array. We present a program transformation that takes a program P to an equivalent program P' such that, by verifying P' instead of P, we can reduce the burden of the exponential explosion in the number of case splits. Here, the case splits are according to whether two statements using the same map variable are independent or not; if they are independent, we might as well employ two different map variables and thus remove the need for a case split (this is the idea behind the program transformation). We have implemented the program transformation and show that, in an ideal case, we can avoid the exponential explosion.
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