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Combination of pose and rank consensus in docking-based virtual screening: the best of both worlds.

ABSTRACT: The use of high-throughput docking (HTD) in the drug discovery pipeline is today widely established. In spite of methodological improvements in docking accuracy (pose prediction), scoring power, ranking power, and screening power in HTD remain challenging. In fact, pose prediction is of critical importance in view of the pose-dependent scoring process, since incorrect poses will necessarily decrease the ranking power of scoring functions. The combination of results from different docking programs (consensus scoring) has been shown to improve the performance of HTD. Moreover, it has been also shown that a pose consensus approach might also result in database enrichment. We present a new methodology named Pose/Ranking Consensus (PRC) that combines both pose and ranking consensus approaches, to overcome the limitations of each stand-alone strategy. This approach has been developed using four docking programs (ICM, rDock, Auto Dock 4, and PLANTS; the first one is commercial, the other three are free). We undertook a thorough analysis for the best way of combining pose and rank strategies, and applied the PRC to a wide range of 34 targets sampling different protein families and binding site properties. Our approach exhibits an improved systematic performance in terms of enrichment factor and hit rate with respect to either pose consensus or consensus ranking alone strategies at a lower computational cost, while always ensuring the recovery of a suitable number of ligands. An analysis using four free docking programs (replacing ICM by Auto Dock Vina) displayed comparable results.

SUBMITTER: Scardino V

PROVIDER: S-EPMC8965822 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Abstract Biceps tendinopathy and superior labrum anterior posterior lesions are a common source of shoulder pain and disability and can be effectively treated with biceps tenodesis. There are a variety of open and arthroscopic tenodesis techniques, but no one technique has demonstrated superiority. Arthroscopic techniques often disregard the extra-articular portions of the biceps tendon as a potential source of pain. Open techniques address this concern; however, they can be associated with wound complications, increased blood loss, nerve injury, and disruptions to surgical workflow. Here, we describe an all arthroscopic tenodesis technique at the suprapectoral zone of the tendon. This method addresses extra-articular sources of pain, while limiting the potential pitfalls of open surgery. Technique Video Video 1 Narrated technique video. Standard posterior, anterior, lateral, and low anterior portals are used during the technique. Viewing from the posterior portal in a right shoulder the biceps anchor is debrided to a stable base. A BirdBeak device is inserted through the standard anterior portal and pierces the biceps tendon as laterally as possible, and an 18-gauge spinal needle is used to tease the suture from the BirdBeak device. After a standard subacromial decompression is performed the camera is inserted into the standard lateral portal, and an anterior subdeltoid bursectomy is performed to provide adequate visualization of the tenodesis site. An accessory low anterior portal is created about 1.5 cm proximal to the pectoralis major tendon insertion. The pectoralis major insertion site is used to aid in localization of the tendon just proximal to the subdeltoid portion of the tendon. An 11-blade is inserted through the low anterior portal and used to incise the transverse humeral ligament; the biceps tendon will often bulge from beneath the ligament at this step, confirming appropriate position. The bicep tendon is retracted with the probe, and a noncannulated 8-mm reamer is inserted into the low anterior portal and used to produce a unicortical tunnel. The tunnel’s edges are debrided using an arthroscopic shaver and the arthroscopic electrocautery device; the inferior portion of the tunnel must be smooth to prevent fraying of the tendon. The biceps tendon is then tensioned appropriately via tension pulled through the previously placed suture. A fork-tipped interference screw is then introduced through the low anterior portal to introduce the biceps tendon into the tenodesis site. The interference screw is then inserted and left 1 mm proud. The residual proximal bicep tendon is then amputated using an arthroscopic biter and removed through the lateral portal. The finished tenodesis site is probed and inspected, and a standard postoperative protocol is used.

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Combination of pose and rank consensus in docking-based virtual screening: the best of both worlds.

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