Integrative GWAS and co-localisation analysis suggests novel genes associated with age-related multimorbidity.

West CE, Karim M, Falaguera MJ, Speidel L, Green CJ, Logie L, Schwartzentruber J, Ochoa D, Lord JM, Ferguson MAJ, Bountra C, Wilkinson GF, Vaughan B, Leach AR, Dunham I, Marsden BD.

Sci Data, 2023

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Genome-wide association analysis and Mendelian randomization proteomics identify drug targets for heart failure.

Rasooly D, Peloso GM, Pereira AC, Dashti H, Giambartolomei C, Wheeler E, Aung N, Ferolito BR, Pietzner M, Farber-Eger EH, Wells QS, Kosik NM, Gaziano L, Posner DC, Bento AP, Hui Q, Liu C, Aragam K, Wang Z, Charest B, Huffman JE, Wilson PWF, Phillips LS, Whittaker J, Munroe PB, Petersen SE, Cho K, Leach AR, Magariños MP, Gaziano JM, VA Million Veteran Program, Langenberg C, Sun YV, Joseph J, Casas JP.

Nat Commun, 2023

doi:10.1038/s41467-023-39253-3.

Applications of single-cell RNA sequencing in drug discovery and development.

Van de Sande B, Lee JS, Mutasa-Gottgens E, Naughton B, Bacon W, Manning J, Wang Y, Pollard J, Mendez M, Hill J, Kumar N, Cao X, Chen X, Khaladkar M, Wen J, Leach A, Ferran E.

Nat Rev Drug Discov, 2023

doi:10.1038/s41573-023-00688-4.

EMBL's European Bioinformatics Institute (EMBL-EBI) in 2022.

Thakur M, Bateman A, Brooksbank C, Freeberg M, Harrison M, Hartley M, Keane T, Kleywegt G, Leach A, Levchenko M, Morgan S, McDonagh EM, Orchard S, Papatheodorou I, Velankar S, Vizcaino JA, Witham R, Zdrazil B, McEntyre J.

Nucleic Acids Res, 2023

doi:10.1093/nar/gkac1098.

Integrative analysis of GWAS and co-localisation data suggests novel genes associated with age-related multimorbidity

West CE, Karim M, Falaguera MJ, Speidel L, Green CJ, Logie L, Schwartzentruber J, Ochoa D, Lord JM, Ferguson MAJ, Bountra C, Wilkinson GF, Vaughan B, Leach AR, Dunham I, Marsden BD.

2022

doi:10.1101/2022.11.11.22282236.

Illuminating the Druggable Genome through Patent Bioactivity Data

Magariños MP, Gaulton A, Félix E, Kizilören T, Arcila R, Oprea T, Leach AR.

2022

doi:10.1101/2022.07.15.500187.

CACHE (Critical Assessment of Computational Hit-finding Experiments): A public-private partnership benchmarking initiative to enable the development of computational methods for hit-finding.

Ackloo S, Al-Awar R, Amaro RE, Arrowsmith CH, Azevedo H, Batey RA, Bengio Y, Betz UAK, Bologa CG, Chodera JD, Cornell WD, Dunham I, Ecker GF, Edfeldt K, Edwards AM, Gilson MK, Gordijo CR, Hessler G, Hillisch A, Hogner A, Irwin JJ, Jansen JM, Kuhn D, Leach AR, Lee AA, Lessel U, Morgan MR, Moult J, Muegge I, Oprea TI, Perry BG, Riley P, Rousseaux SAL, Saikatendu KS, Santhakumar V, Schapira M, Scholten C, Todd MH, Vedadi M, Volkamer A, Willson TM.

Nat Rev Chem, 2022

doi:10.1038/s41570-022-00363-z.

Genome-wide association analysis and Mendelian randomization proteomics identify drug targets for heart failure

Rasooly D, Peloso GM, Pereira AC, Dashti H, Giambartolomei C, Wheeler E, Aung N, Ferolito BR, Pietzner M, Farber-Eger EH, Wells QS, Kosik NM, Gaziano L, Posner DC, Bento AP, Hui Q, Liu C, Aragam K, Wang Z, Charest B, Huffman JE, Wilson PW, Phillips LS, Whittaker J, Munroe PB, Petersen SE, Cho K, Leach AR, Magariños MP, Gaziano JM, Langenberg C, Sun YV, Joseph J, Casas JP, VA Million Veteran Program.

2022

doi:10.1101/2022.04.14.22273877.

Target 2035 - update on the quest for a probe for every protein.

Müller S, Ackloo S, Al Chawaf A, Al-Lazikani B, Antolin A, Baell JB, Beck H, Beedie S, Betz UAK, Bezerra GA, Brennan PE, Brown D, Brown PJ, Bullock AN, Carter AJ, Chaikuad A, Chaineau M, Ciulli A, Collins I, Dreher J, Drewry D, Edfeldt K, Edwards AM, Egner U, Frye SV, Fuchs SM, Hall MD, Hartung IV, Hillisch A, Hitchcock SH, Homan E, Kannan N, Kiefer JR, Knapp S, Kostic M, Kubicek S, Leach AR, Lindemann S, Marsden BD, Matsui H, Meier JL, Merk D, Michel M, Morgan MR, Mueller-Fahrnow A, Owen DR, Perry BG, Rosenberg SH, Saikatendu KS, Schapira M, Scholten C, Sharma S, Simeonov A, Sundström M, Superti-Furga G, Todd MH, Tredup C, Vedadi M, von Delft F, Willson TM, Winter GE, Workman P, Arrowsmith CH.

RSC Med Chem, 2022

doi:10.1039/d1md00228g.

The Enzyme Portal: an integrative tool for enzyme information and analysis.

Zaru R, Onwubiko J, Ribeiro AJM, Cochrane K, Tyzack JD, Muthukrishnan V, Pravda L, Thornton JM, O'Donovan C, Velanker S, Orchard S, Leach A, Martin MJ.

FEBS J, 2022

doi:10.1111/febs.16168.

Influence of HLA Class II Polymorphism on Predicted Cellular Immunity Against SARS-CoV-2 at the Population and Individual Level.

Copley HC, Gragert L, Leach AR, Kosmoliaptsis V.

Front Immunol, 2021

doi:10.3389/fimmu.2021.669357.

The PROTACtable genome.

Schneider M, Radoux CJ, Hercules A, Ochoa D, Dunham I, Zalmas LP, Hessler G, Ruf S, Shanmugasundaram V, Hann MM, Thomas PJ, Queisser MA, Benowitz AB, Brown K, Leach AR.

Nat Rev Drug Discov, 2021

doi:10.1038/s41573-021-00245-x.

Target-Based Evaluation of "Drug-Like" Properties and Ligand Efficiencies.

Leeson PD, Bento AP, Gaulton A, Hersey A, Manners EJ, Radoux CJ, Leach AR.

J Med Chem, 2021

doi:10.1021/acs.jmedchem.1c00416.

Actionable druggable genome-wide Mendelian randomization identifies repurposing opportunities for COVID-19.

Gaziano L, Giambartolomei C, Pereira AC, Gaulton A, Posner DC, Swanson SA, Ho YL, Iyengar SK, Kosik NM, Vujkovic M, Gagnon DR, Bento AP, Barrio-Hernandez I, Rönnblom L, Hagberg N, Lundtoft C, Langenberg C, Pietzner M, Valentine D, Gustincich S, Tartaglia GG, Allara E, Surendran P, Burgess S, Zhao JH, Peters JE, Prins BP, Angelantonio ED, Devineni P, Shi Y, Lynch KE, DuVall SL, Garcon H, Thomann LO, Zhou JJ, Gorman BR, Huffman JE, O'Donnell CJ, Tsao PS, Beckham JC, Pyarajan S, Muralidhar S, Huang GD, Ramoni R, Beltrao P, Danesh J, Hung AM, Chang KM, Sun YV, Joseph J, Leach AR, Edwards TL, Cho K, Gaziano JM, Butterworth AS, Casas JP, VA Million Veteran Program COVID-19 Science Initiative.

Nat Med, 2021

doi:10.1038/s41591-021-01310-z.

MAIP: a web service for predicting blood-stage malaria inhibitors.

Bosc N, Felix E, Arcila R, Mendez D, Saunders MR, Green DVS, Ochoada J, Shelat AA, Martin EJ, Iyer P, Engkvist O, Verras A, Duffy J, Burrows J, Gardner JMF, Leach AR.

J Cheminform, 2021

doi:10.1186/s13321-021-00487-2.

Drug Safety Data Curation and Modeling in ChEMBL: Boxed Warnings and Withdrawn Drugs.

Hunter FMI, Bento AP, Bosc N, Gaulton A, Hersey A, Leach AR.

Chem Res Toxicol, 2021

doi:10.1021/acs.chemrestox.0c00296.

An open source chemical structure curation pipeline using RDKit.

Bento AP, Hersey A, Félix E, Landrum G, Gaulton A, Atkinson F, Bellis LJ, De Veij M, Leach AR.

J Cheminform, 2020

doi:10.1186/s13321-020-00456-1.

Influence of HLA class II polymorphism on predicted cellular immunity against SARS-CoV-2 at the population and individual level

Copley HC, Gragert L, Leach AR, Kosmoliaptsis V.

2020

doi:10.1101/2020.12.24.424326.

Actionable druggable genome-wide Mendelian randomization identifies repurposing opportunities for COVID-19

Gaziano L, Giambartolomei C, Pereira AC, Gaulton A, Posner DC, Swanson SA, Ho Y, Iyengar SK, Kosik NM, Vujkovic M, Gagnon DR, Bento AP, Beltrao P, Barrio-Hernandez I, Rönnblom L, Hagberg N, Lundtoft C, Langenberg C, Pietzner M, Valentine D, Allara E, Surendran P, Burgess S, Zhao JH, Peters JE, Prins BP, Danesh J, Devineni P, Shi Y, Lynch KE, DuVall SL, Garcon H, Thomann LO, Zhou JJ, Gorman BR, Huffman JE, O’Donnell CJ, Tsao PS, Beckham JC, Pyarajan S, Muralidhar S, Huang GD, Ramoni R, Hung AM, Chang K, Sun YV, Joseph J, Leach AR, Edwards TL, Cho K, Gaziano JM, Butterworth AS, Casas JP.

2020

doi:10.1101/2020.11.19.20234120.

MAIP: A web service for predicting blood-stage malaria inhibitors

Bosc N, Felix E, Arcila R, Mendez D, Saunders M, Green D, Ochoada J, Shelat A, Martin E, Iyer P, Engkvist O, Verras A, Duffy J, Burrows J, Gardner M, Leach A.

2020

doi:10.21203/rs.3.rs-41814/v2.

An Open Source Chemical Structure Curation Pipeline using RDKit

Bento AP, Hersey A, Felix E, Landrum G, Gaulton A, Atkinson F, Bellis LJ, De Veij M, Leach AR.

2020

doi:10.21203/rs.3.rs-34715/v2.

The Global Phosphorylation Landscape of SARS-CoV-2 Infection.

Bouhaddou M, Memon D, Meyer B, White KM, Rezelj VV, Correa Marrero M, Polacco BJ, Melnyk JE, Ulferts S, Kaake RM, Batra J, Richards AL, Stevenson E, Gordon DE, Rojc A, Obernier K, Fabius JM, Soucheray M, Miorin L, Moreno E, Koh C, Tran QD, Hardy A, Robinot R, Vallet T, Nilsson-Payant BE, Hernandez-Armenta C, Dunham A, Weigang S, Knerr J, Modak M, Quintero D, Zhou Y, Dugourd A, Valdeolivas A, Patil T, Li Q, Hüttenhain R, Cakir M, Muralidharan M, Kim M, Jang G, Tutuncuoglu B, Hiatt J, Guo JZ, Xu J, Bouhaddou S, Mathy CJP, Gaulton A, Manners EJ, Félix E, Shi Y, Goff M, Lim JK, McBride T, O'Neal MC, Cai Y, Chang JCJ, Broadhurst DJ, Klippsten S, De Wit E, Leach AR, Kortemme T, Shoichet B, Ott M, Saez-Rodriguez J, tenOever BR, Mullins RD, Fischer ER, Kochs G, Grosse R, García-Sastre A, Vignuzzi M, Johnson JR, Shokat KM, Swaney DL, Beltrao P, Krogan NJ.

Cell, 2020

doi:10.1016/j.cell.2020.06.034.

Drug mechanism-of-action discovery through the integration of pharmacological and CRISPR screens.

Gonçalves E, Segura-Cabrera A, Pacini C, Picco G, Behan FM, Jaaks P, Coker EA, van der Meer D, Barthorpe A, Lightfoot H, Mironenko T, Beck A, Richardson L, Yang W, Lleshi E, Hall J, Tolley C, Hall C, Mali I, Thomas F, Morris J, Leach AR, Lynch JT, Sidders B, Crafter C, Iorio F, Fawell S, Garnett MJ.

Mol Syst Biol, 2020

doi:10.15252/msb.20199405.

Hotspots API: A Python Package for the Detection of Small Molecule Binding Hotspots and Application to Structure-Based Drug Design.

Curran PR, Radoux CJ, Smilova MD, Sykes RA, Higueruelo AP, Bradley AR, Marsden BD, Spring DR, Blundell TL, Leach AR, Pitt WR, Cole JC.

J Chem Inf Model, 2020

doi:10.1021/acs.jcim.9b00996.

Drug mechanism-of-action discovery through the integration of pharmacological and CRISPR screens

Gonçalves E, Segura-Cabrera A, Pacini C, Picco G, Behan FM, Jaaks P, Coker EA, van der Meer D, Barthorpe A, Lightfoot H, Leach AR, Lynch JT, Sidders B, Crafter C, Iorio F, Fawell S, Garnett MJ, GDSC Screening Team.

2020

doi:10.1101/2020.01.14.905729.

Large scale comparison of QSAR and conformal prediction methods and their applications in drug discovery.

Bosc N, Atkinson F, Felix E, Gaulton A, Hersey A, Leach AR.

J Cheminform, 2019

doi:10.1186/s13321-018-0325-4.

ChEMBL: towards direct deposition of bioassay data.

Mendez D, Gaulton A, Bento AP, Chambers J, De Veij M, Félix E, Magariños MP, Mosquera JF, Mutowo P, Nowotka M, Gordillo-Marañón M, Hunter F, Junco L, Mugumbate G, Rodriguez-Lopez M, Atkinson F, Bosc N, Radoux CJ, Segura-Cabrera A, Hersey A, Leach AR.

Nucleic Acids Res, 2019

doi:10.1093/nar/gky1075.

Comparative genomics of the major parasitic worms.

International Helminth Genomes Consortium.

Nat Genet, 2019

doi:10.1038/s41588-018-0262-1.

A large-scale dataset of in vivo pharmacology assay results.

Hunter FMI, L Atkinson F, Bento AP, Bosc N, Gaulton A, Hersey A, Leach AR.

Sci Data, 2018

doi:10.1038/sdata.2018.230.

Unexplored therapeutic opportunities in the human genome.

Oprea TI, Bologa CG, Brunak S, Campbell A, Gan GN, Gaulton A, Gomez SM, Guha R, Hersey A, Holmes J, Jadhav A, Jensen LJ, Johnson GL, Karlson A, Leach AR, Ma'ayan A, Malovannaya A, Mani S, Mathias SL, McManus MT, Meehan TF, von Mering C, Muthas D, Nguyen DT, Overington JP, Papadatos G, Qin J, Reich C, Roth BL, Schürer SC, Simeonov A, Sklar LA, Southall N, Tomita S, Tudose I, Ursu O, Vidovic D, Waller A, Westergaard D, Yang JJ, Zahoránszky-Köhalmi G.

Nat Rev Drug Discov, 2018

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Unexplored therapeutic opportunities in the human genome.

Oprea TI, Bologa CG, Brunak S, Campbell A, Gan GN, Gaulton A, Gomez SM, Guha R, Hersey A, Holmes J, Jadhav A, Jensen LJ, Johnson GL, Karlson A, Leach AR, Ma'ayan A, Malovannaya A, Mani S, Mathias SL, McManus MT, Meehan TF, von Mering C, Muthas D, Nguyen DT, Overington JP, Papadatos G, Qin J, Reich C, Roth BL, Schürer SC, Simeonov A, Sklar LA, Southall N, Tomita S, Tudose I, Ursu O, Vidovic D, Waller A, Westergaard D, Yang JJ, Zahoránszky-Köhalmi G.

Nat Rev Drug Discov, 2018

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Drug Target Commons: A Community Effort to Build a Consensus Knowledge Base for Drug-Target Interactions.

Tang J, Tanoli ZU, Ravikumar B, Alam Z, Rebane A, Vähä-Koskela M, Peddinti G, van Adrichem AJ, Wakkinen J, Jaiswal A, Karjalainen E, Gautam P, He L, Parri E, Khan S, Gupta A, Ali M, Yetukuri L, Gustavsson AL, Seashore-Ludlow B, Hersey A, Leach AR, Overington JP, Repasky G, Wennerberg K, Aittokallio T.

Cell Chem Biol, 2018

doi:10.1016/j.chembiol.2017.11.009.

Using ChEMBL web services for building applications and data processing workflows relevant to drug discovery.

Nowotka MM, Gaulton A, Mendez D, Bento AP, Hersey A, Leach A.

Expert Opin Drug Discov, 2017

doi:10.1080/17460441.2017.1339032.

The ChEMBL database in 2017.

Gaulton A, Hersey A, Nowotka M, Bento AP, Chambers J, Mendez D, Mutowo P, Atkinson F, Bellis LJ, Cibrián-Uhalte E, Davies M, Dedman N, Karlsson A, Magariños MP, Overington JP, Papadatos G, Smit I, Leach AR.

Nucleic Acids Res, 2017

doi:10.1093/nar/gkw1074.

An analysis of the attrition of drug candidates from four major pharmaceutical companies.

Waring MJ, Arrowsmith J, Leach AR, Leeson PD, Mandrell S, Owen RM, Pairaudeau G, Pennie WD, Pickett SD, Wang J, Wallace O, Weir A.

Nat Rev Drug Discov, 2015

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Reprint of: Characterising hepatic mitochondrial function as a model for systemic toxicity: a commentary.

Leach AR, Wallace K, Alepee N, Daston G, Humphris C, Manou I, Modi S, Ringeissen S, Whelan M, Kimber I.

Toxicology, 2012

doi:10.1016/j.tox.2012.10.007.

Characterising hepatic mitochondrial function as a model for systemic toxicity: a commentary.

Leach AR, Wallace K, Alepee N, Daston G, Humphris C, Manou I, Modi S, Ringeissen S, Whelan M, Kimber I.

Toxicology, 2012

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Computer-aided molecular design under the SWOTlight.

Green DV, Leach AR, Head MS.

J Comput Aided Mol Des, 2012

doi:10.1007/s10822-011-9514-1.

Molecular complexity and fragment-based drug discovery: ten years on.

Leach AR, Hann MM.

Curr Opin Chem Biol, 2011

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Cheminformatics and computational chemistry in lead optimisation

Leach A.

J Cheminform, 2011

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Three-dimensional pharmacophore methods in drug discovery.

Leach AR, Gillet VJ, Lewis RA, Taylor R.

J Med Chem, 2010

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A comparison of field-based similarity searching methods: CatShape, FBSS, and ROCS.

Moffat K, Gillet VJ, Whittle M, Bravi G, Leach AR.

J Chem Inf Model, 2008

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Fragment screening: an introduction.

Leach AR, Hann MM, Burrows JN, Griffen EJ.

Mol Biosyst, 2006

doi:10.1039/b610069b.

Prediction of protein-ligand interactions. Docking and scoring: successes and gaps.

Leach AR, Shoichet BK, Peishoff CE.

J Med Chem, 2006

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Design and synthesis of orally active pyrrolidin-2-one-based factor Xa inhibitors.

Watson NS, Brown D, Campbell M, Chan C, Chaudry L, Convery MA, Fenwick R, Hamblin JN, Haslam C, Kelly HA, King NP, Kurtis CL, Leach AR, Manchee GR, Mason AM, Mitchell C, Patel C, Patel VK, Senger S, Shah GP, Weston HE, Whitworth C, Young RJ.

Bioorg Med Chem Lett, 2006

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Analysis and optimization of structure-based virtual screening protocols. (3). New methods and old problems in scoring function design.

Smith R, Hubbard RE, Gschwend DA, Leach AR, Good AC.

J Mol Graph Model, 2003

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A comparison of the pharmacophore identification programs: Catalyst, DISCO and GASP.

Patel Y, Gillet VJ, Bravi G, Leach AR.

J Comput Aided Mol Des, 2002

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Prediction of biological activity for high-throughput screening using binary kernel discrimination.

Harper G, Bradshaw J, Gittins JC, Green DV, Leach AR.

J Chem Inf Comput Sci, 2001

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Molecular complexity and its impact on the probability of finding leads for drug discovery.

Hann MM, Leach AR, Harper G.

J Chem Inf Comput Sci, 2001

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The in silico world of virtual libraries.

Leach AR, Hann MM.

Drug Discov Today, 2000

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PLUMS: a program for the rapid optimization of focused libraries.

Bravi G, Green DV, Hann MM, Leach AR.

J Chem Inf Comput Sci, 2000

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Synergy between combinatorial chemistry and de novo design.

Leach AR, Bryce RA, Robinson AJ.

J Mol Graph Model, 2000

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Where are the GaPs? A rational approach to monomer acquisition and selection.

Leach AR, Green DV, Hann MM, Judd DB, Good AC.

J Chem Inf Comput Sci, 2000

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Ligand solvation in molecular docking.

Shoichet BK, Leach AR, Kuntz ID.

Proteins, 1999

doi:10.1002/(sici)1097-0134(19990101)34:1<4::aid-prot2>3.0.co;2-6.

Implementation of a system for reagent selection and library enumeration, profiling, and design.

Leach AR, Bradshaw J, Green DV, Hann MM, Delany JJ.

J Chem Inf Comput Sci, 1999

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Binding constants of neuraminidase inhibitors: An investigation of the linear interaction energy method.

Wall ID, Leach AR, Salt DW, Ford MG, Essex JW.

J Med Chem, 1999

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Exploring the conformational space of protein side chains using dead-end elimination and the A* algorithm.

Leach AR, Lemon AP.

Proteins, 1998

doi:10.1002/(sici)1097-0134(19981101)33:2<227::aid-prot7>3.0.co;2-f.

Structure-based selection of building blocks for array synthesis via the World-Wide Web.

Leach AR.

J Mol Graph Model, 1997

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Development and validation of a genetic algorithm for flexible docking.

Jones G, Willett P, Glen RC, Leach AR, Taylor R.

J Mol Biol, 1997

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The aggregation behaviour of two structurally isomeric glycolipids.

Attard GS, Blackaby WP, Leach AR.

Chem Phys Lipids, 1994

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Current methods for site-directed structure generation.

Lewis RA, Leach AR.

J Comput Aided Mol Des, 1994

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Automated molecular design: a new fragment-joining algorithm.

Leach AR, Kilvington SR.

J Comput Aided Mol Des, 1994

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Ligand docking to proteins with discrete side-chain flexibility.

Leach AR.

J Mol Biol, 1994

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Constitutional, configurational and conformational analysis of transition metal coordination complexes.

Leach AR.

J Comput Aided Mol Des, 1993

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Enantioselective N-oxygenation of chlorpheniramine by the flavin-containing monooxygenase from hog liver.

Cashman JR, Celestial JR, Leach AR.

Xenobiotica, 1992

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Automated conformational analysis: algorithms for the efficient construction of low-energy conformations.

Leach AR, Prout K, Dolata DP.

J Comput Aided Mol Des, 1990

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Automated conformational analysis and structure generation: algorithms for molecular perception.

Leach AR, Dolata DP, Prout K.

J Chem Inf Comput Sci, 1990

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An investigation into the construction of molecular models by the template joining method.

Leach AR, Prout K, Dolata DP.

J Comput Aided Mol Des, 1988

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WIZARD: AI in conformational analysis.

Dolata DP, Leach AR, Prout K.

J Comput Aided Mol Des, 1987

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