Dataset Information

Weighted Implementation of Suboptimal Paths (WISP): An Optimized Algorithm and Tool for Dynamical Network Analysis.

ABSTRACT: Allostery can occur by way of subtle cooperation among protein residues (e.g., amino acids) even in the absence of large conformational shifts. Dynamical network analysis has been used to model this cooperation, helping to computationally explain how binding to an allosteric site can impact the behavior of a primary site many ångstroms away. Traditionally, computational efforts have focused on the most optimal path of correlated motions leading from the allosteric to the primary active site. We present a program called Weighted Implementation of Suboptimal Paths (WISP) capable of rapidly identifying additional suboptimal pathways that may also play important roles in the transmission of allosteric signals. Aside from providing signal redundancy, suboptimal paths traverse residues that, if disrupted through pharmacological or mutational means, could modulate the allosteric regulation of important drug targets. To demonstrate the utility of our program, we present a case study describing the allostery of HisH-HisF, an amidotransferase from T. maritima thermotiga. WISP and its VMD-based graphical user interface (GUI) can be downloaded from http://nbcr.ucsd.edu/wisp.

SUBMITTER: Van Wart AT

PROVIDER: S-EPMC3958135 | biostudies-literature | 2014 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Weighted Implementation of Suboptimal Paths (WISP): An Optimized Algorithm and Tool for Dynamical Network Analysis.

Van Wart Adam T AT Durrant Jacob J Votapka Lane L Amaro Rommie E RE

Journal of chemical theory and computation 20140114 2

Allostery can occur by way of subtle cooperation among protein residues (e.g., amino acids) even in the absence of large conformational shifts. Dynamical network analysis has been used to model this cooperation, helping to computationally explain how binding to an allosteric site can impact the behavior of a primary site many ångstroms away. Traditionally, computational efforts have focused on the most optimal path of correlated motions leading from the allosteric to the primary active site. We ...[more]

PMID: 24803851

Similar Datasets

Project description:BackgroundImplementation methods of risk-stratified cancer screening guidance throughout a health care system remains understudied.ObjectiveConduct a preliminary analysis of the implementation of a risk-stratified prostate cancer screening algorithm in a single health care system.DesignComparison of men seen pre-implementation (2/1/2016-2/1/2017) vs. post-implementation (2/2/2017-2/21/2018).ParticipantsMen, aged 40-75 years, without a history of prostate cancer, who were seen by a primary care provider.InterventionsThe algorithm was integrated into two components in the electronic health record (EHR): in Health Maintenance as a personalized screening reminder and in tailored messages to providers that accompanied prostate-specific antigen (PSA) results.Main measuresPrimary outcomes: percent of men who met screening algorithm criteria; percent of men with a PSA result. Logistic repeated measures mixed models were used to test for differences in the proportion of individuals that met screening criteria in the pre- and post-implementation periods with age, race, family history, and PSA level included as covariates.Key resultsDuring the pre- and post-implementation periods, 49,053 and 49,980 men, respectively, were seen across 26 clinics (20.6% African American). The proportion of men who met screening algorithm criteria increased from 49.3% (pre-implementation) to 68.0% (post-implementation) (p < 0.001); this increase was observed across all races, age groups, and primary care clinics. Importantly, the percent of men who had a PSA did not change: 55.3% pre-implementation, 55.0% post-implementation. The adjusted odds of meeting algorithm-based screening was 6.5-times higher in the post-implementation period than in the pre-implementation period (95% confidence interval, 5.97 to 7.05).ConclusionsIn this preliminary analysis, following implementation of an EHR-based algorithm, we observed a rapid change in practice with an increase in screening in higher-risk groups balanced with a decrease in screening in low-risk groups. Future efforts will evaluate costs and downstream outcomes of this strategy.

Dataset Information

Weighted Implementation of Suboptimal Paths (WISP): An Optimized Algorithm and Tool for Dynamical Network Analysis.

Publications

Weighted Implementation of Suboptimal Paths (WISP): An Optimized Algorithm and Tool for Dynamical Network Analysis.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets