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Virtual screening with AutoDock: theory and practice

Sandro Cosconati, Stefano Forli, Alex L Perryman, Rodney Harris, David S Goodsell, Arthur J Olson
2010 Expert Opinion on Drug Discovery  
doi:10.1517/17460441.2010.484460 pmid:21532931 pmcid:PMC3083070 fatcat:3e4feyhwuzcb7i7mcmj4t6wiua

Robust Scoring Functions for Protein–Ligand Interactions with Quantum Chemical Charge Models

Jui-Chih Wang, Jung-Hsin Lin, Chung-Ming Chen, Alex L. Perryman, Arthur J. Olson
2011 Journal of Chemical Information and Modeling  
Ordinary least square (OLS) regression has been used widely for constructing the free scoring functions for protein-ligand interaction. However, OLS is very sensitive to the existence of outliers, and models constructed using it are easily affected by the outliers or even the choice of the dataset. On the other hand, determination of atomic charges is regarded as of central importance, because the electrostatic interaction is known to be a key contributing factor for biomolecular association.
more » ... the development of the AutoDock4 scoring function, only OLS was conducted, and the simple Gasteiger method was adopted. It is therefore of considerable interest to see whether more rigorous charge models could improve the statistical performance of the AutoDock4 scoring function. In this study, we have employed two well-established quantum chemical approaches, namely the restrained electrostatic potential (RESP) and the Austin-Model 1-Bond Charge Correction (AM1-BCC) methods, to obtain atomic partial charges, and we have compared how different charge models affect the performance of AutoDock4 scoring functions. In combination with robust regression analysis and outlier exclusion, our new protein-ligand free energy regression model with AM1-BCC charges for ligands and Amber99SB charges for proteins achieve lowest root-mean squared error of 1.637 kcal/mol for the training set of 147 complexes and 2.176 kcal/mol for the external test set of 1427 complexes. The assessment for binding pose prediction with the 100 external decoy sets indicates very high success rate of 87% with the criteria of predicted RMSD less than 2 Å. The success rates and statistical performance of our robust scoring functions are only weakly class-dependent (hydrophobic, hydrophilic, or mixed). Supporting Information Available: Outliers detected by the robust regression analysis in three charge model combinations were listed. The plots of dipole moment distributions and prediction errors in the training set were provided. This information is available free of charge via the Internet at METHODS Functional form of AutoDock4 Scoring function Improvements of the AutoDock4 (AD4) scoring function 9 over its predecessor, AutoDock3, 8 include a refined functional form of the desolvation energy, more atom types, and a significantly larger training dataset. The AD4 scoring function comprises five energetic terms: the van der Waals interaction, hydrogen bonding, electrostatic interaction, desolvation energy, and torsional entropy. The AD4 scoring function predicts the binding free energy with the following formula: Wang et al.
doi:10.1021/ci200220v pmid:21932857 pmcid:PMC4639406 fatcat:rdoo7hsr45b63lhcr6h3nu7zxi

A Dynamic Model of HIV Integrase Inhibition and Drug Resistance

Alex L. Perryman, Stefano Forli, Garrett M. Morris, Catherine Burt, Yuhui Cheng, Michael J. Palmer, Kevin Whitby, J. Andrew McCammon, Chris Phillips, Arthur J. Olson
2010 Journal of Molecular Biology  
Maria L.  ...  Please cite this article as: Perryman, A. L., et al., A Dynamic Model of HIV Integrase Inhibition and Drug Resistance, J. Mol. Biol. (2010), doi:10.1016/j.jmb.2010.01.033  ...  However, HIV integrase inhibitors such as the pioneering compounds L-731,988 and S-1360 contain structural features consistent with a two-metal chelation motif. 2, 3 Subsequently, a planar two-metal  ... 
doi:10.1016/j.jmb.2010.01.033 pmid:20096702 pmcid:PMC2846753 fatcat:p52dxrakg5cxnkexyaay2oagw4

Machine Learning Model Analysis and Data Visualization with Small Molecules Tested in a Mouse Model of Mycobacterium tuberculosis Infection (2014–2015)

Sean Ekins, Alexander L. Perryman, Alex M. Clark, Robert C. Reynolds, Joel S. Freundlich
2016 Journal of Chemical Information and Modeling  
The renewed urgency to develop new treatments for Mycobacterium tuberculosis (Mtb) infection has resulted in large-scale phenotypic screening and thousands of new active compounds in vitro. The next challenge is to identify candidates to pursue in a mouse in vivo efficacy model as a step to predicting clinical efficacy. We previously analyzed over 70 years of this mouse in vivo efficacy data, which we used to generate and validate machine learning models. Curation of 60 additional small
more » ... s with in vivo data published in 2014 and 2015 was undertaken to further test these models. This represents a much larger test set than for the previous models. Several computational approaches have now been applied to analyze these molecules and compare their molecular properties beyond those attempted previously. Our previous machine learning models have been updated, and a novel aspect has been added in the form of mouse liver microsomal half-life (MLM t 1/2 ) and in vitro-based Mtb models incorporating cytotoxicity data that were used to predict in vivo activity for comparison. Our best Mtb in vivo models possess fivefold ROC values > 0.7, sensitivity > 80%, and concordance > 60%, while the best specificity value is >40%. Use of an MLM t 1/2 Bayesian model affords comparable results for scoring the 60 compounds tested. Combining MLM stability and in vitro Mtb models in a novel consensus workflow in the best cases has a positive predicted value (hit rate) > 77%. Our results indicate that Bayesian models constructed with literature in vivo Mtb data generated by different laboratories in various mouse models can have predictive value and may be used alongside MLM t 1/2 and in vitrobased Mtb models to assist in selecting antitubercular compounds with desirable in vivo efficacy. We demonstrate for the first time that consensus models of any kind can be used to predict in vivo activity for Mtb. In addition, we describe a new clustering method for data visualization and apply this to the in vivo training and test data, ultimately making the method accessible in a mobile app.
doi:10.1021/acs.jcim.6b00004 pmid:27335215 pmcid:PMC4962118 fatcat:ej2wwtdjmncbpgo3ok4sibff3u

Page 366 of The Kansas Historical Quarterly Vol. 3, Issue 4 [page]

1934 The Kansas Historical Quarterly  
Porter L. C. Perryman ( G. W. Grayson, Secretary J. M. Perryman (resigned) S. W. Perryman Oktarharsars-harjo Charke Timothy Barnett 1 J. M. C. Smith G. W.  ...  Folsom Maha tubber Alfred Wright Alex R. Durant Coleman Cole— oe at * ee  ... 


Margaret A Hoogland, Erin D. Foster, Carol L. Perryman
2021 Hypothesis : the newsletter of the Research Section of MLA  
Erin was joined by Carol Perryman in 2018 as Co-Editor and in 2020, Margaret Hoogland was recruited to serve as Co-Editor while Erin transitioned out of her role.  ...  In January 2021, Alexandria (Alex) Quesenberry Wilson joined the Social Media Team for Hypothesis.  ...  Additionally, Alex is an up-and-coming researcher, who was a recipient of an MLA 2021 Research Caucus Award. Wishing them the best!  ... 
doi:10.18060/25775 fatcat:uolkozwo3rhbxggcpaaltobw6i

Page 600 of Sage Family Studies Abstracts Vol. 29, Issue 4 [page]

2007 Sage Family Studies Abstracts  
, 1196 Perry, Robin E., 0818, 0819 Perryman, Heidi, 0265 Perryman, Heidi P., 0255 Persico, Michele, 1104 Persson, Lars Ake, 0128 Pérusse, Daniel, 0411 Peters Razza, Rachel, 0410 Peterson, Brennan D., 0879  ...  Pianta, Robert C., 0384 Pierce, Robert, 0185 Pierce-Jordan, Sandra, 0084 Piercy, Fred P., 0338 Piercy, Kathleen W., 0140 Pike, Alison, 0141 Pike, Lisbeth T., 1162 Pinazo, Sacramento, 0768, 0869 Piquero, Alex  ... 

Page 3 of Armed Forces Chemical Journal Vol. 1, Issue 3 [page]

1947 Armed Forces Chemical Journal  
Smith, Perryman, Anthony E. Silveira, Jr., Edge- wood; Charles E. Jones, Kingsville; Llewellyn S. Dando, Baltimore; Stanley L. Ray, Franklinville; Harry Shannon, Joppa; Charles P.  ...  Dwaayer, Edge- wood; Joseph L. Hughes, Perryman; Harrison Gross, Joppa; Armand VY. Motsinger, Aberdeen; Jacob G. Nissely, Edgewood Arsenal; Quincy Walker, Edgewood; Charles J. Kolb, Baltimore.  ... 

Page 768 of The Veterinary Record Vol. 22, Issue 1142 [page]

1910 The Veterinary Record  
L. Harrison, A. Rogerson, W. Roger Clarke, Prof. H. A. Woodruff, and Hugh A. MacCormack, Hon. Sec. ; and as visitors: Messrs. Thomas Maben and Alex. Crabb. MINUTES.  ...  Perryman suggested for that condition. Mr.  ... 

Page 276 of The Veterinary Record Vol. 22, Issue 1111 [page]

1909 The Veterinary Record  
Perryman, R. J. Foreman, Ainsworth Wilson, Prof. Macqueen, Sidney Villar, J. Willett, A. L. Butters, J. Rowe, H. King, P. W. D. Smith, and Captain A. Olver. Mr.  ...  Alex. Todd, Worthing; and M. E. White, Ports- mouth ; with Mr. H. Leeney, Southwick, a visitor. On the proposition of Prof. Wooldridge, seconded by Mr. A.  ... 

Page 283 of Geophysics Vol. 11, Issue 2 [page]

1946 Geophysics  
Finnigan, Thomas L. Flude, J. W. Fohs, F. Julius Frosch, Alex Frowe, Eugene Futral, John E. Gardner, Derry H. George, Fred W. Gibson, M. O Giezendanner, S. S. Gilmore, John A.  ...  Pasley, L. C. Payne, J. E. Pernell, J. H. Perryman, J. D. Peters, Jack W. Pittman, C. V. A. Pratt, R. B. Ransom, J. H. Ransone, W. R. Raper, W. B. Reagor, Edward C. Reeves, J. R. Ranner, Darwin S.  ... 

Page 254 of Geophysics Vol. 7, Issue 2 [page]

1942 Geophysics  
Paslay, L. C. Pernell, J. H. Perryman, J. D. Pittman, C. V. A. Poindexter, Louis Pollard, J. C. Pollei, Donald W. Pratt, R. B. Ransone, W. R. Reagor, Edward C. Renner, Darwin S. Rice, E. R., Jr.  ...  Frosch, Alex Gahagan, Donald I. Gallie, J. F Gardner, Derry H. Garrett, L. P. Gibson, M. O. Gilmore, John A. Golden, John M. Goldstone, Frank Gomez, J. S Goss, Henry V. Griffin, I. M., Jr.  ... 

Page 502 of The Veterinary Record Vol. 18, Issue 915 [page]

1906 The Veterinary Record  
Lowe Walter Perryman Chas. Sheather ist e has oblige on. Sec.  ...  L. Weighill W. D. Rees eg W. A. Pallin Col. Chas. Steel Mr. H. K. Roberts R. Rimmer Jas. Douglas J. F. Thurston T. W. Cave J. Alex. Todd T. Ludlow ‘Messrs. J. Bell and Son Grasby and Reynolds Mr. J.  ... 

Page 389 of American Spirit Vol. 59, Issue 6 [page]

1925 American Spirit  
Execs. were sons Alex. (from recs in Pa. Arch. Alex. d unmar.) & Wm. Bogle. Wife Eliz. sons Alex. & Wm.  ...  He has Runyan data DEPARTMENT 380 and may be able to assist you—Miss L. L. Runyon, 123 South St., Warrensburg, Mo. ConNELL.  ... 

Page 108 of Art Institute of Chicago. Bulletin of the Art Institute of Chicago Vol. 21, Issue 8 [page]

1927 Art Institute of Chicago. Bulletin of the Art Institute of Chicago  
James L. Nichols Orlando Noble Mrs. W. E. Nunamaker Mrs. Margaret H. Peterson Mrs. Hattie S. Perryman Mrs. Henry Posner Jacob H. Press Mrs. Charles Butler Price Mrs. George E.  ...  Alex Field A. J. Filkins Charles H. Fischer Mrs. Henry P. Fitzpatrick Mrs. Ignatius T. Fitzpatrick Louis Flader Allen L. Fox Miss Emily Allen Frake William Francis A. Richard Frank Mrs.  ... 
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