32 research outputs found
Real-time Optimized Rendezvous on Nonholonomic Resource-Constrained Robots
Abstract In this work, we consider a group of differential-wheeled robots endowed with noisy relative positioning capabilities. We develop a decentralized approach based on a receding horizon controller to generate, in real-time, trajectories that guarantee the convergence of our robots to a common location (i.e. rendezvous). Our receding horizon controller is tailored around two numerical optimization methods: the hybrid-state A * and trust-region algorithms. To validate both methods and test their robustness to computational delays, we perform exhaustive experiments on a team of four real mobile robots equipped with relative positioning hardware
Activation of the Cannabinoid CB1 Receptor May Involve a W6.48/F3.36 Rotamer Toggle Switch
The cannabinoid CB1 receptor, a member of the Rhodopsin (Rho) family of G protein coupled receptors (GPCRs), exhibits high levels of constitutive activity. In contrast, Rho exhibits an exquisite lack of constitutive activity. In Rho, W6.48(265) on transmembrane helix 6 (TMH6) is flanked by aromatic residues at positions i-4 (F6.44) and i + 3 (Y6.51), while in CB1 the residues i-4 and i + 3 to W6.48 are leucines (L6.44 and L6.51). Based upon spectroscopic evidence, W6.48 has been proposed to undergo a rotamer switch (χ1 g+ →trans) upon activation of Rho. In the work reported here, the biased Monte Carlo method, Conformational Memories (CM) was used to test the hypothesis that the high constitutive activity exhibited by CB1 may be due, in part, to the lack of aromatic residues i-4 and i + 3 from W6.48. In this work, the W6.48 rotamer shift (χ1 g+ →trans) was used as the criterion for activation. Conformational Memories (CM) calculations on WT CB1 TMH6 and L6.44F and L6.51Y mutant TMH6s revealed that an aromatic residue at 6.44 tends to disfavor the W6.48 χ1 g+ →trans transition and an aromatic residue at 6.51 would require a concomitant movement of the Y6.51 χ1 from trans→g+ when the W6.48 χ1 undergoes a g+ →trans shift. In contrast, CM calculations on WT CB1 TMH6 revealed that the presence of leucines at 6.44 and 6.51 provide W6.48 with greater conformational mobility, with a W6.48 transχ1 preferred. Conformational Memories calculations also revealed that the W6.48 χ1 g+ →trans transition in WT CB1 TMH6 is correlated with the degree of kinking in TMH6. The average proline kink angles for TMH6 were higher for helices with a W6.48 g+ χ1 than for those with a W6.48 transχ1. These results are consistent with experimental evidence that TMH6 straightens during activation. Transmembrane helix (TMH) bundle models of the inactive (R) and active (R*) states of CB1 were then probed for interactions that may constrain W6.48 in the inactive state of CB1. These studies revealed that F3.36 (transχ1) helps to constrain W6.48 in a g+ χ1 in the inactive (R) state of CB1. In the R* state, these studies suggest that F3.36 must assume a g+ χ1 in order to allow W6.48 to shift to a transχ1. These results suggest that the W6.48/F3.36 interaction may act as the ‘toggle switch’ for CB1 activation, with W6.48 χ1 g+/F3.36 χ1 trans representing the inactive (R) and W6.48 χ1 trans/F3.36 χ1 g+ representing the active (R*) state of CB1