Assessment of programs for ligand binding affinity prediction.
RyangGuk Kim,Jeffrey Skolnick +1 more
TLDR
FlexX, X‐Score, AutoDock, and BLEEP programs examined for their performance in binding free energy prediction in various situations including cocrystallized complex structures, cross docking of ligands to their non‐cocrystallized receptors, docking of thermally unfolded receptor decoys to their ligands, and complex structures with “randomized” ligand decoys.Abstract:
The prediction of the binding free energy between a ligand and a protein is an important component in the virtual screening and lead optimization of ligands for drug discovery. To determine the quality of current binding free energy estimation programs, we examined FlexX, X-Score, AutoDock, and BLEEP for their performance in binding free energy prediction in various situations including cocrystallized complex structures, cross docking of ligands to their non-cocrystallized receptors, docking of thermally unfolded receptor decoys to their ligands, and complex structures with "randomized" ligand decoys. In no case was there a satisfactory correlation between the experimental and estimated binding free energies over all the datasets tested. Meanwhile, a strong correlation between ligand molecular weight-binding affinity correlation and experimental predicted binding affinity correlation was found. Sometimes the programs also correctly ranked ligands' binding affinities even though native interactions between the ligands and their receptors were essentially lost because of receptor deformation or ligand randomization, and the programs could not decisively discriminate randomized ligand decoys from their native ligands; this suggested that the tested programs miss important components for the accurate capture of specific ligand binding interactions.read more
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Advances and Challenges in Protein-Ligand Docking
Sheng-You Huang,Xiaoqin Zou +1 more
TL;DR: Recent advances of protein flexibility, ligand sampling, and scoring functions—the three important aspects in protein-ligand docking are reviewed.
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Receptor–ligand molecular docking
TL;DR: The main topics and recent computational and methodological advances in protein–ligand docking are summarised, including protein flexibility, multiple ligand binding modes and the free-energy landscape profile for binding affinity prediction.
Journal ArticleDOI
Comparative Assessment of Scoring Functions on an Updated Benchmark: 2. Evaluation Methods and General Results
TL;DR: The results obtained suggest that the real challenge in protein-ligand binding affinity prediction lies in polar interactions and associated desolvation effect and nonadditive features observed among high-affinity protein- ligand complexes also need attention.
References
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TL;DR: The results of an international collaboration to produce and make freely available a draft sequence of the human genome are reported and an initial analysis is presented, describing some of the insights that can be gleaned from the sequence.
Journal ArticleDOI
Automated docking using a Lamarckian genetic algorithm and an empirical binding free energy function
Garrett M. Morris,David S. Goodsell,Robert Scott Halliday,Ruth Huey,William E. Hart,Richard K. Belew,Arthur J. Olson +6 more
TL;DR: It is shown that both the traditional and Lamarckian genetic algorithms can handle ligands with more degrees of freedom than the simulated annealing method used in earlier versions of AUTODOCK, and that the Lamarckia genetic algorithm is the most efficient, reliable, and successful of the three.
Journal ArticleDOI
Initial sequencing and comparative analysis of the mouse genome.
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TL;DR: The results of an international collaboration to produce a high-quality draft sequence of the mouse genome are reported and an initial comparative analysis of the Mouse and human genomes is presented, describing some of the insights that can be gleaned from the two sequences.
Journal ArticleDOI
The genome sequence of Drosophila melanogaster
Mark Raymond Adams,Susan E. Celniker,Robert A. Holt,Cheryl A. Evans,Jeannine D. Gocayne,Peter Amanatides,Steve Scherer,Peter W. Li,Roger A. Hoskins,R. Galle,Reed A. George,Suzanna E. Lewis,Stephen Richards,Michael Ashburner,Scott Henderson,Granger G. Sutton,Jennifer R. Wortman,Mark Yandell,Qing Zhang,Lin Chen,Rhonda C. Brandon,Yu-Hui Rogers,R. Blazej,Mark Champe,Barret D. Pfeiffer,Kenneth H. Wan,Colleen Doyle,E. G. Baxter,Gregg Helt,Catherine R. Nelson,G. L. Gabor Miklos,Josep F. Abril,A. Agbayani,Huijin An,C. Andrews-Pfannkoch,Danita Baldwin,Richard M. Ballew,Anand Basu,James Baxendale,Leyla Bayraktaroglu,Ellen M. Beasley,Karen Beeson,Panayiotis V. Benos,Benjamin P. Berman,D. Bhandari,Slava Bolshakov,Dana Borkova,Michael R. Botchan,John Bouck,Peter Brokstein,Philippe Brottier,Kenneth C. Burtis,Dana A. Busam,Heather Butler,Edouard Cadieu,I. Chandra,J. Michael Cherry,Simon Cawley,Carl Dahlke,Lionel Davenport,P. Davies,B. de Pablos,Arthur L. Delcher,Zuoming Deng,A. Deslattes Mays,Ian M. Dew,Susanne Dietz,Kristina Dodson,Lisa Doup,Michael Downes,Shannon Dugan-Rocha,B. C. Dunkov,Patrick J. Dunn,K. J. Durbin,Carlos Evangelista,Concepcion Ferraz,Steven Ferriera,Wolfgang Fleischmann,Carl Fosler,Andrei Gabrielian,Neha Garg,William M. Gelbart,Kenneth Glasser,A. Glodek,Fangcheng Gong,J. Harley Gorrell,Zhiping Gu,Ping Guan,Michael Harris,Nomi L. Harris,Damon A. Harvey,Thomas J. Heiman,Judith Hernandez,Jarrett Houck,Damon Hostin,K. Houston,Timothy Howland,Ming-Hui Wei,Chinyere Ibegwam,M. Jalali,Francis Kalush,Gary H. Karpen,Zhaoxi Ke,James A. Kennison,K. A. Ketchum,B. E. Kimmel,Chinnappa D. Kodira,Cheryl L. Kraft,Saul A. Kravitz,David Kulp,Zhongwu Lai,Paul Lasko,Yiding Lei,Alexander Levitsky,Jun Li,Zhenya Li,Yunye Liang,Xiaoying Lin,Xiangjun Liu,B. Mattei,Tina C. McIntosh,Michael P. McLeod,D. McPherson,Gennady V. Merkulov,Natalia Milshina,Clark M. Mobarry,J. Morris,A. Moshrefi,Stephen M. Mount,Mee Moy,Brian Murphy,Lee Murphy,Donna M. Muzny,David L. Nelson,David R. Nelson,Keith Nelson,K. Nixon,Deborah R. Nusskern,Joanne Pacleb,Michael J. Palazzolo,G. S. Pittman,Sue Pan,J. Pollard,Vinita Puri,Martin G. Reese,Knut Reinert,Karin A. Remington,Robert D. C. Saunders,Robert D. C. Saunders,F. Scheeler,H. Shen,B. Christopher Shue,Inga Siden-Kiamos,Michael Simpson,Marian P. Skupski,Thomas J. Smith,Eugene G. Spier,Allan C. Spradling,Mark Stapleton,Renee Strong,E. Sun,Robert Svirskas,C. Tector,Russell Turner,Eli Venter,Aihui Wang,Xianyuan Wang,Zhen Yuan Wang,David A. Wassarman,George M. Weinstock,Jean Weissenbach,Sherita Williams,Trevor Woodage,Kim C. Worley,D. Wu,Shih-Hung Yang,Q. Alison Yao,Jane Ye,R. F. Yeh,Jayshree Zaveri,Ming Zhan,Gefei Zhang,Qi Zhao,Liansheng Zheng,Xiangqun Zheng,Fei Zhong,Wenyan Zhong,X. Zhou,Shiaoping C. Zhu,Xiancan Zhu,Hamilton O. Smith,Richard A. Gibbs,Eugene W. Myers,Gerald M. Rubin,J. Craig Venter +194 more
TL;DR: The nucleotide sequence of nearly all of the approximately 120-megabase euchromatic portion of the Drosophila genome is determined using a whole-genome shotgun sequencing strategy supported by extensive clone-based sequence and a high-quality bacterial artificial chromosome physical map.
Journal ArticleDOI
Development and validation of a genetic algorithm for flexible docking.
TL;DR: GOLD (Genetic Optimisation for Ligand Docking) is an automated ligand docking program that uses a genetic algorithm to explore the full range of ligand conformational flexibility with partial flexibility of the protein, and satisfies the fundamental requirement that the ligand must displace loosely bound water on binding.