Benchmarking the Performance of Irregular Computations in AutoDock-GPU Molecular Docking.

Irregular applications can be found in different scientific fields. In computer-aided drug design, molecular docking simulations play an important role in finding promising drug candidates. AutoDock is a software application widely used for predicting molecular interactions at close distances. It is characterized by irregular computations and long execution runtimes. In recent years, a hardware-accelerated version of AutoDock, called AutoDock-GPU, has been under active development. This work benchmarks the recent code and algorithmic enhancements incorporated into AutoDock-GPU. Particularly, we analyze the impact on execution runtime of techniques based on early termination. These enable AutoDock-GPU to explore the molecular space as necessary, while safely avoiding redundant computations. Our results indicate that it is possible to achieve average runtime reductions of 50% by using these techniques. Furthermore, a comprehensive literature review is also provided, where our work is compared to relevant approaches leveraging hardware acceleration for molecular docking.

GPU-Accelerated Molecular Dynamics and Free Energy Methods in Amber18: Performance Enhancements and New Features.

We report progress in graphics processing unit (GPU)-accelerated molecular dynamics and free energy methods in Amber18. Of particular interest is the development of alchemical free energy algorithms, including free energy perturbation and thermodynamic integration methods with support for nonlinear soft-core potential and parameter interpolation transformation pathways. These methods can be used in conjunction with enhanced sampling techniques such as replica exchange, constant-pH molecular dynamics, and new 12-6-4 potentials for metal ions. Additional performance enhancements have been made that enable appreciable speed-up on GPUs relative to the previous software release.

GPU-Accelerated Drug Discovery with Docking on the Summit Supercomputer: Porting, Optimization, and Application to COVID-19 Research.

Protein-ligand docking is an in silico tool used to screen potential drug compounds for their ability to bind to a given protein receptor within a drug-discovery campaign. Experimental drug screening is expensive and time consuming, and it is desirable to carry out large scale docking calculations in a high-throughput manner to narrow the experimental search space. Few of the existing computational docking tools were designed with high performance computing in mind. Therefore, optimizations to maximize use of high-performance computational resources available at leadership-class computing facilities enables these facilities to be leveraged for drug discovery. Here we present the porting, optimization, and validation of the AutoDock-GPU program for the Summit supercomputer, and its application to initial compound screening efforts to target proteins of the SARS-CoV-2 virus responsible for the current COVID-19 pandemic.

Accelerating molecular dynamic simulation on graphics processing units.

We describe a complete implementation of all-atom protein molecular dynamics running entirely on a graphics processing unit (GPU), including all standard force field terms, integration, constraints, and implicit solvent. We discuss the design of our algorithms and important optimizations needed to fully take advantage of a GPU. We evaluate its performance, and show that it can be more than 700 times faster than a conventional implementation running on a single CPU core.

Reliability of a telephone-based Glasgow Outcome Scale assessment using a structured interview in a heterogenous population of patients and examiners.

A reliable telephone-based Glasgow Outcome Scale (GOS) assessment would be advantageous to both patients and investigators. Using a previously published structured GOS interview and scoring system, the aim of this study was to assess the reliability of telephone-based GOS scores compared to those obtained face-to-face in a heterogenous population of patients and examiners. Sixty-six patients hospitalized for a variety of acute neurological injuries underwent two GOS interviews approximately 90 days after injury. From a pool of six examiners, structured interviews were conducted using a standardized data form containing nine yes/no questions. One interview was conducted face-to-face and the other interview was conducted by telephone, the order being randomly selected. A different examiner conducted the second interview, and was unaware of the findings of the first interview. From this data, a separate investigator assigned GOS scores using standardized criteria. Concordant GOS scores were obtained in 71% (47/66) of patients and discordant scores in 29% (19/66); kappa = 0.56 +/- 0.08 (SE) (95% CI kappa = 0.40-0.73). Patient-, examiner-, and interview-related characteristics had no significant associations with GOS concordance, although patient sex had a significant association with discrepant responses to one specific question (work at previous capacity). When used by multiple examiners to assess patients with diverse neurological conditions, use of a structured GOS examination does not guarantee a reliable telephone-based GOS score. Determination of whether patient sex influences the validity of the structured face-to-face GOS interview is worthy of future study.

Craniocervical motion during direct laryngoscopy and orotracheal intubation with the Macintosh and Miller blades: an in vivo cinefluoroscopic study.

BACKGROUND: Previous studies have characterized segmental craniocervical motion that occurs during direct laryngoscopy and intubation with a Macintosh laryngoscope blade. Comparable studies with the Miller blade have not been performed. The aim of this study was to compare maximal segmental craniocervical motion occurring during direct laryngoscopy and orotracheal intubation with Macintosh and Miller blades. METHODS: Eleven anesthetized and pharmacologically paralyzed patients underwent two sequential orotracheal intubations, one with a Macintosh blade and another with a Miller in random order. During each intubation, segmental craniocervical motion from the occiput to the fifth cervical vertebra (C5) was recorded using continuous lateral cinefluoroscopy. Single-frame images corresponding to the point of maximal cervical motion for both blade types were compared with a preintubation image. Using image analysis software, angular change in the sagittal plane at each of five intervertebral segments was compared between the Macintosh and Miller blades. RESULTS: Extension at occiput-C1 was greater with the Macintosh blade compared with the Miller (12.1 degrees +/- 4.9 degrees vs. 9.5 degrees +/- 3.8 degrees, respectively; mean difference = 2.7 degrees +/- 3.0 degrees; P = 0.012). Total craniocervical extension (occiput-C5) was also greater with the Macintosh blade compared with the Miller (28.1 degrees +/- 9.5 degrees vs. 23.2 degrees +/- 8.4 degrees, respectively; mean difference = 4.8 degrees +/- 4.4 degrees; P = 0.008). CONCLUSIONS: Compared with the Macintosh, the Miller blade was associated with a statistically significant, but quantitatively small, decrease in cervical extension. This difference is likely too small to be important in routine practice.

Neuropsychological executive functions of adolescent sex offenders and nonsex offenders.

A growing body of research now suggests that a substantial number of criminal offenders display neuropsychological deficits, especially frontal-executive dysfunctions. The present study investigated the possibility of similar deficits by comparing the performance of 60 adolescent sex offenders court-ordered to a residential treatment facility with the performance of 60 nonsexual delinquent offenders matched on several pertinent sociodemographic characteristics and scores on four neuropsychological tests: (1) the Trail Making Test, (2) the Controlled Oral Word Association test of the Multilingual Aphasia Examination, (3) the Tower of London, and (4) the Wisconsin Card-sorting Test. Analysis indicated a pattern of frontal-executive dysfunction in a subset of both groups of offenders; this pattern has both theoretical and treatment implications.