Dataset Information

ALiBERO: evolving a team of complementary pocket conformations rather than a single leader.

ABSTRACT: Docking and virtual screening (VS) reach maximum potential when the receptor displays the structural changes needed for accurate ligand binding. Unfortunately, these conformational changes are often poorly represented in experimental structures or homology models, debilitating their docking performance. Recently, we have shown that receptors optimized with our LiBERO method (Ligand-guided Backbone Ensemble Receptor Optimization) were able to better discriminate active ligands from inactives in flexible-ligand VS docking experiments. The LiBERO method relies on the use of ligand information for selecting the best performing individual pockets from ensembles derived from normal-mode analysis or Monte Carlo. Here we present ALiBERO, a new computational tool that has expanded the pocket selection from single to multiple, allowing for automatic iteration of the sampling-selection procedure. The selection of pockets is performed by a dual method that uses exhaustive combinatorial search plus individual addition of pockets, selecting only those that maximize the discrimination of known actives compounds from decoys. The resulting optimized pockets showed increased VS performance when later used in much larger unrelated test sets consisting of biologically active and inactive ligands. In this paper we will describe the design and implementation of the algorithm, using as a reference the human estrogen receptor alpha.

SUBMITTER: Rueda M

PROVIDER: S-EPMC3478405 | biostudies-literature | 2012 Oct

REPOSITORIES: biostudies-literature

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ALiBERO: evolving a team of complementary pocket conformations rather than a single leader.

Rueda Manuel M Totrov Max M Abagyan Ruben R

Journal of chemical information and modeling 20120917 10

Docking and virtual screening (VS) reach maximum potential when the receptor displays the structural changes needed for accurate ligand binding. Unfortunately, these conformational changes are often poorly represented in experimental structures or homology models, debilitating their docking performance. Recently, we have shown that receptors optimized with our LiBERO method (Ligand-guided Backbone Ensemble Receptor Optimization) were able to better discriminate active ligands from inactives in f ...[more]

PMID: 22947092

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Project description:BACKGROUND:The incidence of cardiac arrests per year in the United States continues to increase, yet in-hospital cardiac arrest survival rates significantly vary between hospitals. Current methods of training are expensive, time consuming, and difficult to scale, which necessitates improvements in advanced cardiac life support (ACLS) training. Virtual reality (VR) has been proposed as an alternative or adjunct to high-fidelity simulation (HFS) in several environments. No evaluations to date have explored the ability of a VR program to examine both technical and behavioral skills and demonstrate a cost comparison. OBJECTIVE:This study aimed to explore the utility of a voice-based VR ACLS team leader refresher as compared with HFS. METHODS:This prospective observational study performed at an academic institution consisted of 25 postgraduate year 2 residents. Participants were randomized to HFS or VR training and then crossed groups after a 2-week washout. Participants were graded on technical and nontechnical skills. Participants also completed self-assessments about the modules. Proctors were assessed for fatigue and task saturation, and cost analysis based on local economic data was performed. RESULTS:A total of 23 of 25 participants were included in the scoring analysis. Fewer participants were familiar with VR compared with HFS (9/25, 36% vs 25/25, 100%; P<.001). Self-reported satisfaction and utilization scores were similar; however, significantly more participants felt HFS provided better feedback: 99 (IQR 89-100) vs 79 (IQR 71-88); P<.001. Technical scores were higher in the HFS group; however, nontechnical scores for decision making and communication were not significantly different between modalities. VR sessions were 21 (IQR 19-24) min shorter than HFS sessions, the National Aeronautics and Space Administration task load index scores for proctors were lower in each category, and VR sessions were estimated to be US $103.68 less expensive in a single-learner, single-session model. CONCLUSIONS:Utilization of a VR-based team leader refresher for ACLS skills is comparable with HFS in several areas, including learner satisfaction. The VR module was more cost-effective and was easier to proctor; however, HFS was better at delivering feedback to participants. Optimal education strategies likely contain elements of both modalities. Further studies are needed to examine the utility of VR-based environments at scale.

Dataset Information

ALiBERO: evolving a team of complementary pocket conformations rather than a single leader.

Publications

ALiBERO: evolving a team of complementary pocket conformations rather than a single leader.

Similar Datasets

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