Conformational transitions upon ligand binding: Holo-structure prediction from apo conformations.

Biological function of proteins is frequently associated with the formation of complexes with small-molecule ligands. Experimental structure determination of such complexes at atomic resolution, however, can be time-consuming and costly. Computational methods for structure prediction of protein/ligand complexes, particularly docking, are as yet restricted by their limited consideration of receptor flexibility, rendering them not applicable for predicting protein/ligand complexes if large conformational changes of the receptor upon ligand binding are involved. Accurate receptor models in the ligandbound state (holo structures), however, are a prerequisite for successful structure-based drug design. Hence, if only an unbound (apo) structure is available distinct from the ligand-bound conformation, structure-based drug design is severely limited. We present a method to predict the structure of protein/ligand complexes based solely on the apo structure, the ligand and the radius of gyration of the holo structure. The method is applied to ten cases in which proteins undergo structural rearrangements of up to 7.1 A ˚ backbone RMSD upon ligand binding. In all cases, receptor models within 1.6 A˚ backbone RMSD to the target were predicted and close-to-native ligand binding poses were obtained for 8 of 10 cases in the top-ranked complex models. A protocol is presented that is expected to enable structure modeling of protein/ligand complexes and structure-based drug design for cases where crystal structures of ligand-bound conformations are no

Loop space homology associated with the mod 2 Dickson invariants

Peer reviewedPublisher PD

No variations in transit times for Qatar-1 b

The transiting hot Jupiter planet Qatar-1 b was presented to exhibit variations in transit times that could be of perturbative nature. A hot Jupiter with a planetary companion on a nearby orbit would constitute an unprecedented planetary configuration, important for theories of formation and evolution of planetary systems. We performed a photometric follow-up campaign to confirm or refute transit timing variations. We extend the baseline of transit observations by acquiring 18 new transit light curves acquired with 0.6-2.0 m telescopes. These photometric time series, together with data available in the literature, were analyzed in a homogenous way to derive reliable transit parameters and their uncertainties. We show that the dataset of transit times is consistent with a linear ephemeris leaving no hint for any periodic variations with a range of 1 min. We find no compelling evidence for the existence of a close-in planetary companion to Qatar-1 b. This finding is in line with a paradigm that hot Jupiters are not components of compact multi-planetary systems. Based on dynamical simulations, we place tighter constraints on a mass of any fictitious nearby planet in the system. Furthermore, new transit light curves allowed us to redetermine system parameters with the precision better than that reported in previous studies. Our values generally agree with previous determinations.Comment: Accepted for publication in A&