Ultrafast protein structure-based virtual screening with Panther

Abstract

Molecular docking is by far the most common method used in protein structure-based virtual screening. This paper presents Panther, a novel ultrafast multipurpose docking tool. In Panther, a simple shape-electrostatic model of the ligand-binding area of the protein is created by utilizing the protein crystal structure. The features of the possible ligands are then compared to the model by using a similarity search algorithm. On average, one ligand can be processed in a few minutes by using classical docking methods, whereas using Panther processing takes <1 s. The presented Panther protocol can be used in several applications, such as speeding up the early phases of drug discovery projects, reducing the number of failures in the clinical phase of the drug development process, and estimating the environmental toxicity of chemicals. Panther-code is available in our web pages (http://www.jyu.fi/panther) free of charge after registration.

Reliability analysis and optimization of the consensus docking approach for the development of virtual screening studies

“…Docking is also largely used for hit identification, representing the main example of receptor-based virtual screening (VS) procedure: a docking-based approach is commonly reported in several successful VS studies, both alone and in combination with other computational strategies [4][5][6][7][8] . For these reasons, the exponential attention that docking is gaining over time, as proved by the number of novel docking procedures and scoring functions reported in literature only in the last few years, cannot be blamed [9][10][11][12][13][14][15][16][17][18][19][20] . However, the remarkable interest for docking and for the development of new and optimized approaches is mainly due to the fact that the prediction of the actual binding mode of a ligand into a protein target is still far from being an easy task.…”

2016 EMBO Chemical Biology Conference

“…Employing mechanism‐ and structure‐based design, 5′‐ O ‐( N ‐salicylsulfamoyl)adenosine (salicyl‐AMS) was shown to inhibit a key adenylation enzyme that is involved in siderophore biosynthesis in Mycobacterium tuberculosis, with demonstrated efficacy in mouse models of tuberculosis . Olli Pentikäinen (University of Jyväskylä) described virtual‐screening approaches that were associated with rapid execution and excellent success rate for the systems under study . The next speaker was Stephanie Heinzlmeir from Bernhard Kuster's lab (Technical University Munich).…”

“…[4] Olli Pentikäinen (University of Jyväskylä)described virtual-screening approaches that were associated with rapid execution and excellents uccess rate for the systems under study. [5] The next speaker was Stephanie Heinzlmeir from Bernhard Kuster's lab (Technical University Munich). Stephanie reported the application of chemical-proteomics approaches based on Kinobead technology fora ssessing the selectivity of kinase inhibitors.…”

Fragment‐ and negative image‐based screening of phosphodiesterase 10A inhibitors

“…In this regard, the negative image‐based (NIB) screening (Figure ; Figure S1; Ahinko, Kurkinen, Niinivehmas, Pentikäinen, & Postila, ; Lätti, Niinivehmas, & Pentikäinen, ; Niinivehmas, Salokas, Lätti, Raunio, & Pentikäinen, ; Niinivehmas, Virtanen, Lehtonen, Postila, & Pentikäinen, ; Virtanen & Pentikäinen, ) is set to get the best from both worlds as it can be used to screen compounds with only the protein 3D structure and the screening process itself lends its speed from the traditional ligand‐based screening methodology.…”