Improving Docking Performance Using Negative Image-Based Rescoring
Kurkinen, S., Niinivehmas, S., Ahinko, M., Lätti, S., Pentikäinen, O., & Postila, P. (2018). Improving Docking Performance Using Negative Image-Based Rescoring. Frontiers in Pharmacology, 9(March), Article 260. https://doi.org/10.3389/fphar.2018.00260
Published inFrontiers in Pharmacology
© the Authors, 2018. This is an open access article distributed under the terms of the Creative Commons License.
Despite the large computational costs of molecular docking, the default scoring functions are often unable to recognize the active hits from the inactive molecules in large-scale virtual screening experiments. Thus, even though a correct binding pose might be sampled during the docking, the active compound or its biologically relevant pose is not necessarily given high enough score to arouse the attention. Various rescoring and post-processing approaches have emerged for improving the docking performance. Here, it is shown that the very early enrichment (number of actives scored higher than 1% of the highest ranked decoys) can be improved on average 2.5-fold or even 8.7-fold by comparing the docking-based ligand conformers directly against the target protein's cavity shape and electrostatics. The similarity comparison of the conformers is performed without geometry optimization against the negative image of the target protein's ligand-binding cavity using the negative image-based (NIB) screening protocol. The viability of the NIB rescoring or the R-NiB, pioneered in this study, was tested with 11 target proteins using benchmark libraries. By focusing on the shape/electrostatics complementarity of the ligand-receptor association, the R-NiB is able to improve the early enrichment of docking essentially without adding to the computing cost. By implementing consensus scoring, in which the R-NiB and the original docking scoring are weighted for optimal outcome, the early enrichment is improved to a level that facilitates effective drug discovery. Moreover, the use of equal weight from the original docking scoring and the R-NiB scoring improves the yield in most cases. ...
PublisherFrontiers Research Foundation
Publication in research information system
MetadataShow full item record
Except where otherwise noted, this item's license is described as © the Authors, 2018. This is an open access article distributed under the terms of the Creative Commons License.
Showing items with similar title or keywords.
Airborne-laser-scanning-derived auxiliary information discriminating between broadleaf and conifer trees improves the accuracy of models for predicting timber volume in mixed and heterogeneously structured forests Bont, Leo Gallus; Hill, Andreas; Waser, Lars T.; Bürgi, Anton; Ginzler, Christian; Blattert, Clemens (Elsevier, 2020)Managing forests for ecosystem services and biodiversity requires accurate and spatially explicit forest inventory data. A major objective of forest management inventories is to estimate the standing timber volume for ...
Addressing ecological effects of radiation on populations and ecosystems to improve protection of the environment against radiation : agreed statements from a Consensus Symposium Bréchignac, François; Oughton, Deborah; Mays, Claire; Barnthouse, Lawrence; Beasley, James C.; Bonisoli-Alquati, Andrea; Bradshaw, Clare; Brown, Justin; Dray, Stéphane; Geras'kin, Stanislav; Glenn, Travis; Higley, Kathy; Ishida, Ken; Kapustka, Lawrence; Kautsky, Ulrik; Kuhne, Wendy; Lynch, Michael; Mappes, Tapio; Mihok, Steve; Møller, Anders P.; Mothersill, Carmel; Mousseau, Timothy A.; Otaki, Joji; Pryakhin, Evgeny (Elsevier Ltd; International Union of Radioecology, 2016)This paper reports the output of a consensus symposium organized by the International Union of Radioecology in November 2015. The symposium gathered an academically diverse group of 30 scientists to consider the still ...
Automatic social distance estimation for photographic studies : Performance evaluation, test benchmark, and algorithm Seker, Mert; Männistö, Anssi; Iosifidis, Alexandros; Raitoharju, Jenni (Elsevier, 2022)The social distancing regulations introduced to slow down the spread of COVID-19 virus directly affect a basic form of non-verbal communication, and there may be longer term impacts on human behavior and culture that remain ...
Löppönen, Sampsa (2022)Perifeerinen havainnointi on ratkaisevan tärkeää joukkuelajeissa, joissa tarkkaillaan useita pelaajia samanaikaisesti. Aiempi havainnointitutkimus urheilun parissa on keskittynyt tarkan näön alueen rooliin ja sen käyttäytymisen ...
A post-exercise infrared sauna session improves recovery of neuromuscular performance and muscle soreness after resistance exercise training Ahokas, Essi K.; Ihalainen, Johanna; Hanstock, Helen G.; Savolainen, Eero; Kyröläinen, Heikki (Termedia Sp. z.o.o., 2023)The aim of this study was to investigate effects of a single infrared sauna (IRS) session on postexercise recovery of neuromuscular performance, autonomic nervous system function, subjective sleep quality, and muscle ...