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Correcting the impact of docking pose generation error on binding affinity prediction

Hongjian Li, Kwong-Sak Leung, Man-Hon Wong, Pedro J. Ballester
2016 BMC Bioinformatics  
Results: Against commonly-held views, we have found that pose generation error has generally a small impact on the accuracy of binding affinity prediction.  ...  As a result, test set performance after this error-correcting procedure is much closer to that of predicting the binding affinity in the absence of pose generation error (i.e. on crystal structures).  ...  Declaration This work has been carried out thanks to the support of the A*MIDEX grant (  ... 
doi:10.1186/s12859-016-1169-4 pmid:28185549 pmcid:PMC5046193 fatcat:lthn3rirpnggzbagofpbsp6iku

Leveraging nonstructural data to predict structures and affinities of protein–ligand complexes

Joseph M. Paggi, Julia A. Belk, Scott A. Hollingsworth, Nicolas Villanueva, Alexander S. Powers, Mary J. Clark, Augustine G. Chemparathy, Jonathan E. Tynan, Thomas K. Lau, Roger K. Sunahara, Ron O. Dror
2021 Proceedings of the National Academy of Sciences of the United States of America  
We develop a method to predict a ligand's posethe 3D structure of the ligand bound to its target—that leverages a widely available source of information: a list of other ligands that are known to bind  ...  Over the past five decades, tremendous effort has been devoted to computational methods for predicting properties of ligands—i.e., molecules that bind macromolecular targets.  ...  Sohoni for advice and guidance in the early stages of the project, all members of the R.O.D. laboratory for insightful comments, and J. Javitch for providing materials for mutagenesis experiments.  ... 
doi:10.1073/pnas.2112621118 pmid:34921117 pmcid:PMC8713799 fatcat:ympd3n52yrgvtn6nlq4rre6v2i

Accurate calculation of the absolute free energy of binding for drug molecules

Matteo Aldeghi, Alexander Heifetz, Michael J. Bodkin, Stefan Knapp, Philip C. Biggin
2016 Chemical Science  
Free energy calculations based on molecular dynamics and thermodynamic cycles accurately reproduce experimental affinities of diverse bromodomain inhibitors.  ...  For comparison, also the affinities predicted with the docking scoring function are reported. All values are in kcal mol À1 . All errors are one standard deviation.  ...  Introduction One of the "holy grails" of computational drug design is the accurate prediction of the affinity of a drug for its target protein.  ... 
doi:10.1039/c5sc02678d pmid:26798447 pmcid:PMC4700411 fatcat:n2ddvu6uvrabpmxtlj5nhnekza

The impact of cross-docked poses on performance of machine learning classifier for protein–ligand binding pose prediction

Chao Shen, Xueping Hu, Junbo Gao, Xujun Zhang, Haiyang Zhong, Zhe Wang, Lei Xu, Yu Kang, Dongsheng Cao, Tingjun Hou
2021 Journal of Cheminformatics  
AbstractStructure-based drug design depends on the detailed knowledge of the three-dimensional (3D) structures of protein–ligand binding complexes, but accurate prediction of ligand-binding poses is still  ...  the validation through the random splitting or refined-core splitting and the testing on the re-docked or cross-docked poses.  ...  programs, and the impacts of re-docked and cross-docked poses on each other.  ... 
doi:10.1186/s13321-021-00560-w pmid:34656169 fatcat:zkrqs46myjelrg3o2e3heiufqm

Thermodynamic integration to predict host-guest binding affinities

Morgan Lawrenz, Jeff Wereszczynski, Juan Manuel Ortiz-Sánchez, Sara E. Nichols, J. Andrew McCammon
2012 Journal of Computer-Aided Molecular Design  
The predictions included determination of protonation states for both host and guests, docking pose generation, and binding free energy calculations using thermodynamic integration.  ...  An alchemical free energy method with explicit solvent molecular dynamics simulations was applied as part of the blind prediction contest SAMPL3 to calculate binding free energies for seven guests to an  ...  correction.  ... 
doi:10.1007/s10822-012-9542-5 pmid:22350568 pmcid:PMC4113475 fatcat:evfjxpy2rbclbmyawyaudqkwom

Predicting Absolute Ligand Binding Free Energies to a Simple Model Site

David L. Mobley, Alan P. Graves, John D. Chodera, Andrea C. McReynolds, Brian K. Shoichet, Ken A. Dill
2007 Journal of Molecular Biology  
A central challenge in structure-based ligand design is the accurate prediction of binding free energies.  ...  Finally, we examined the impact of holding the protein rigid, as in docking, with a view to learning how approximations made in docking affect accuracy and how they may be improved.  ...  and the reviewers for insightful comments on the manuscript.  ... 
doi:10.1016/j.jmb.2007.06.002 pmid:17599350 pmcid:PMC2104542 fatcat:5o76l2tjbfbmtepwheil6qizka

Leveraging non-structural data to predict structures of protein-ligand complexes [article]

Joseph M Paggi, Julia A Belk, Scott A Hollingsworth, Nicolas Villanueva, Alexander S Powers, Mary J Clark, Augustine G Chemparathy, Jonathan E Tynan, Thomas K Lau, Roger K Sunahara, Ron O Dror
2020 bioRxiv   pre-print
Dozens of computational docking methods have been developed to address this binding pose prediction problem, but they frequently produce inaccurate results.  ...  Here we present a method that substantially improves the accuracy of binding pose prediction by exploiting a widely available source of non-structural information: a list of other ligands that bind the  ...  on ligand binding. 442 Likewise, future work might exploit the affinity of each known binder; we have not done so here 443 to avoid obscuring the general applicability of our method, as the affinity  ... 
doi:10.1101/2020.06.01.128181 fatcat:f3yxq7mlurbxrmaqp3hzbtkilu

Experimentally guided computational antibody affinity maturation with de novo docking modelling and rational design

Daniel A. Cannon, Lu Shan, Qun Du, Lena Shirinian, Keith W. Rickert, Kim L. Rosenthal, Martin Korade, Lilian E. van Vlerken-Ysla, Andrew Buchanan, Tristan J. Vaughan, Melissa M. Damschroder, Bojana Popovic (+1 others)
2019 PLoS Computational Biology  
To our knowledge, this is one of the first examples of the use of homology modelling and protein docking for affinity maturation and represents an approach that can be widely deployed.  ...  to the antigen for structural predictions.  ...  Acknowledgments The authors thank Lori Clarke and Nerea Gibson for their support with reagent generation. Editorial support was provided by Deborah Shuman of AstraZeneca.  ... 
doi:10.1371/journal.pcbi.1006980 pmid:31042706 pmcid:PMC6513101 fatcat:f6t67bfd35dbzcpdzf643x272e

Structure-Based Drug Design: Docking and Scoring

Romano T. Kroemer
2007 Current protein and peptide science  
Approaches to address some of these challenges and the latest developments in the area are presented. Some aspects of the assessment of docking program performance are discussed.  ...  Although the application of docking and scoring has led to some remarkable successes, there are still some major challenges ahead, which are outlined here as well.  ...  assessment of the binding affinity of the surviving poses.  ... 
doi:10.2174/138920307781369382 pmid:17696866 fatcat:5mpy45vfh5bnvgwebl6w3wcqie

D3R grand challenge 2015: Evaluation of protein–ligand pose and affinity predictions

Symon Gathiaka, Shuai Liu, Michael Chiu, Huanwang Yang, Jeanne A. Stuckey, You Na Kang, Jim Delproposto, Ginger Kubish, James B. Dunbar, Heather A. Carlson, Stephen K. Burley, W. Patrick Walters (+3 others)
2016 Journal of Computer-Aided Molecular Design  
The challenges for both target datasets were conducted in two stages, with the first stage testing pose predictions and the capacity to rank compounds by affinity with minimal structural data; and the  ...  second stage testing methods for ranking compounds with knowledge of at least a subset of the ligand-protein poses.  ...  Seth Harris and to Genentech, Inc. for their collaboration and generous donation of the MAP4K4 dataset and Dr. Phil Hadjuk of Abbvie for the HSP90 dataset.  ... 
doi:10.1007/s10822-016-9946-8 pmid:27696240 pmcid:PMC5562487 fatcat:akvv3ttra5d65msjn62jwntsqm

Blind prediction of HIV integrase binding from the SAMPL4 challenge

David L. Mobley, Shuai Liu, Nathan M. Lim, Karisa L. Wymer, Alexander L. Perryman, Stefano Forli, Nanjie Deng, Justin Su, Kim Branson, Arthur J. Olson
2014 Journal of Computer-Aided Molecular Design  
Pose prediction was also quite challenging, in part because inhibitors in the set bind to three different sites, so even identifying the correct binding site was challenging.  ...  NIH Public Access Abstract Here, we give an overview of the protein-ligand binding portion of the SAMPL4 challenge, which focused on predicting binding of HIV integrase inhibitors in the catalytic core  ...  Acknowledgments We acknowledge the financial support of the National Institutes of Health (1R15GM096257-01A1 to DLM and R01 GM073087 and P50 GM103368 to AJO), and computing support from the UCI Green Planet  ... 
doi:10.1007/s10822-014-9723-5 pmid:24595873 pmcid:PMC4331050 fatcat:h22en4cr7fdpll7d3cuyaflcve

VoteDock: Consensus docking method for prediction of protein-ligand interactions

Dariusz Plewczynski, Michał Łażniewski, Marcin Von Grotthuss, Leszek Rychlewski, Krzysztof Ginalski
2010 Journal of Computational Chemistry  
The aim of docking procedure is to predict correct poses of ligand in the binding site of the protein as well as to score them according to the strength of interaction in a reasonable time frame.  ...  In the context of docking problem, several attempts to transfer that approach have been made. However, as the general opinion is that posing is not the main drawback of docking Plewczynski et al.  ...  The authors thank Prof. Iwona Wawer for fruitful discussions and Kamil Steczkiewicz for his help during the preparation of the article.  ... 
doi:10.1002/jcc.21642 pmid:20812324 pmcid:PMC4510457 fatcat:kew2uusgdzchndmdbntkn3xtmq

Predicting Ligand Binding Affinity with Alchemical Free Energy Methods in a Polar Model Binding Site

Sarah E. Boyce, David L. Mobley, Gabriel J. Rocklin, Alan P. Graves, Ken A. Dill, Brian K. Shoichet
2009 Journal of Molecular Biology  
We predicted that eight compounds would bind to the cavity and five would not; 11 of 13 predictions were correct at this level.  ...  We found that predicting accurate affinities and rank-orderings required near-native starting orientations of the ligand in the binding site.  ...  Acknowledgements We thank Michael Mysinger for reading the manuscript.  ... 
doi:10.1016/j.jmb.2009.09.049 pmid:19782087 pmcid:PMC2788029 fatcat:fhdrweb7jvbt7dyv3hc7nyxz5u

Lessons Learned in Empirical Scoring with smina from the CSAR 2011 Benchmarking Exercise

David Ryan Koes, Matthew P. Baumgartner, Carlos J. Camacho
2013 Journal of Chemical Information and Modeling  
Using our general method, the unique capabilities of smina, a set of default interaction terms from AutoDock Vina, and the CSAR (Community Structure-Activity Resource) 2010 dataset, we created a custom  ...  scoring function and evaluated it in the context of the CSAR 2011 benchmarking exercise.  ...  Acknowledgments This work was supported by grant R01GM097082-01 from the National Institutes of Health.  ... 
doi:10.1021/ci300604z pmid:23379370 pmcid:PMC3726561 fatcat:5is3fcqvifbfpbf7ipx5kd2vue

Choosing the Optimal Rigid Receptor for Docking and Scoring in the CSAR 2013/2014 Experiment

Matthew P. Baumgartner, Carlos J. Camacho
2015 Journal of Chemical Information and Modeling  
conformations out of a set of decoy poses, and rank-ordering sets of congeneric compounds based on affinity to a given protein.  ...  For tRNA (m1G37) methyltransferase (TRMD), ranking a set of 31 congeneric binding compounds cross-docked to the optimal receptor resulted in a R 2 = 0.67; whereas, using any other of the 13 receptor structures  ...  This work was supported by the National Institutes of Health [R01GM097082] and Commonwealth of Pennsylvania Department of Health Grant SAP 4100062224.  ... 
doi:10.1021/acs.jcim.5b00338 pmid:26222931 pmcid:PMC4744803 fatcat:d6sfj5nyhbcnbedibw3xunur5y
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