ABSTRACT
Our information-driven docking approach HADDOCK is a consistent top predictor and scorer since the start of its participation in the CAPRI community-wide experiment. This sustained performance is due, in part, to its ability to integrate experimental data and/or bioinformatics information into the modelling process, and also to the overall robustness of the scoring function used to assess and rank the predictions. In the CASP-CAPRI Round 1 scoring experiment we successfully selected acceptable/medium quality models for 18/14 of the 25 targets - a top-ranking performance among all scorers. Considering that for only 20 targets acceptable models were generated by the community, our effective success rate reaches as high as 90% (18/20). This was achieved using the standard HADDOCK scoring function, which, thirteen years after its original publication, still consists of a simple linear combination of intermolecular van der Waals and Coulomb electrostatics energies and an empirically derived desolvation energy term. Despite its simplicity, this scoring function makes sense from a physico-chemical perspective, encoding key aspects of biomolecular recognition. In addition to its success in the scoring experiment, the HADDOCK server takes the first place in the server prediction category, with 16 successful predictions. Much like our scoring protocol, because of the limited time per target, the predictions relied mainly on either an ab initio center-of-mass and symmetry restrained protocol, or on a template-based approach whenever applicable. These results underline the success of our simple but sensible prediction and scoring scheme. Proteins 2017; 85:417-423. © 2016 Wiley Periodicals, Inc.
Subject(s)
Algorithms , Computational Biology/methods , Molecular Docking Simulation/statistics & numerical data , Proteins/chemistry , Benchmarking , Binding Sites , Crystallography, X-Ray , Databases, Protein , Molecular Docking Simulation/methods , Protein Binding , Protein Conformation , Protein Interaction Mapping , Research Design , Software , Static Electricity , Structural Homology, Protein , ThermodynamicsABSTRACT
Momentary lapses in attention frequently impair goal-directed behavior, sometimes with serious consequences. Nevertheless, we lack an integrated view of the brain mechanisms underlying such lapses. By investigating trial-by-trial relationships between brain activity and response time in humans, we determined that attentional lapses begin with reduced prestimulus activity in anterior cingulate and right prefrontal regions involved in controlling attention. Less efficient stimulus processing during attentional lapses was also characterized by less deactivation of a 'default-mode' network, reduced stimulus-evoked sensory activity, and increased activity in widespread regions of frontal and parietal cortex. Finally, consistent with a mechanism for recovering from attentional lapses, increased stimulus-evoked activity in the right inferior frontal gyrus and the right temporal-parietal junction predicted better performance on the next trial. Our findings provide a new, system-wide understanding of the patterns of brain activity that are associated with brief attentional lapses, which informs both theoretical and clinical models of goal-directed behavior.
