OpenABL: A domain-specific language for parallel and distributed agent-based simulations

Agent-based simulations are becoming widespread among scientists from different areas, who use them to model increasingly complex problems. To cope with the growing computational complexity, parallel and distributed implementations have been developed for a wide range of platforms. However, it is difficult to have simulations that are portable to different platforms while still achieving high performance. We present OpenABL, a domain-specific language for portable, high-performance, parallel agent modeling. It comprises an easy-to-program language that relies on high-level abstractions for programmability and explicitly exploits agent parallelism to deliver high performance. A source-to-source compiler translates the input code to a high-level intermediate representation exposing parallelism, locality and synchronization, and, thanks to an architecture based on pluggable backends, generates target code for multi-core CPUs, GPUs, large clusters and cloud systems. OpenABL has been evaluated on six applications from various fields such as ecology, animation, and social sciences. The generated code scales to large clusters and performs similarly to hand-written target-specific code, while requiring significantly fewer lines of codes

Characterization of a K+-induced conformational switch in a human telomeric DNA oligonucleotide using 2-aminopurine fluorescence

Human telomeric DNA consists of tandem repeats of the DNA sequence d(GGGTTA). Oligodeoxynucletotide telomere models such as d[A(GGGTTA)(3)GGG] (Tel22) fold in a cation-dependent manner into quadruplex structures consisting of stacked G-quartets linked by d(TTA) loops. NMR has shown that in Na(+) solutions Tel22 forms a ‘basket’ topology of four antiparallel strands; in contrast, Tel22 in K(+) solutions consists of a mixture of unknown topologies. Our previous studies on the mechanism of folding of Tel22 and similar telomere analogs utilized changes in UV absorption between 270 and 325 nm that report primarily on G-quartet formation and stacking showed that quadruplex formation occurs within milliseconds upon mixing with an appropriate cation. In the current study, we assessed the dynamics and equilibria of folding of specific loops by using Tel22 derivatives in which the dA residues were serially substituted with the fluorescent reporter base, 2-aminopurine (2-AP). Tel22 folding induced by Na(+) or K(+) assessed by changes in 2-AP fluorescence consists of at least three kinetic steps with time constants spanning a range of ms to several hundred seconds. Na(+)-dependent equilibrium titrations of Tel22 folding could be approximated as a cooperative two-state process. In contrast, K(+)-dependent folding curves were biphasic, revealing that different conformational ensembles are present in 1 mM and 30 mM K(+). This conclusion was confirmed by (1)H NMR. Molecular dynamics simulations revealed a K(+) binding pocket in Tel22 located near dA1 that is specific for the so-called hybrid-1 conformation in which strand 1 is in a parallel arrangement. The possible presence of this topologically specific binding site suggests that K(+) may play an allosteric role in regulating telomere conformation and function by modulating quadruplex tertiary structure

Predicting enantioselectivity: Computation as an efficient "experimental" tool for probing enantioselectivity

As a result of the accurate agreement between computation and experiment obtained using default forcefield parameters, the MMFFs forcefield together with a Monte Carlo conformational search method (MCMM/LMCS) and the MINTA free-energy calculation algorithm has been used to probe the enantioselective potential of a new macrocyclic receptor, hence saving time and money on costly experimental procedures

A combined computational and experimental approach for the analysis of the enantioselective potential of a new macrocyclic receptor for N-protected alpha-amino acids

A new macrocyclic receptor incorporating a thiourea moiety has been synthesised. Crystal structures of the macrocycle showed that the receptor has a rigid backbone but the thiourea moiety can orientate itself to bind to a DMSO solvent molecule. Force-field (MMFFs) calculations were performed to model the macrocycle and its binding properties with respect to N-protected amino acids, which were measured experimentally by NMR titration. Binding free energies were calculated by using the mode integration algorithm (MINTA) or free-energy perturbation (FEP). Excellent qualitative agreement with experiment was obtained. To further exploit the accuracy of the free-energy predictions for this system, the faster free-energy algorithm MINTA was used as a prediction tool to test the binding affinity of the macrocycle towards a series of several other amino acid derivatives, which speeded up considerably the screening process and reduced laboratory costs