SLIDE

Introduction

MSU SLIDE ('Screening for Ligands by Induced-fit Docking, Efficiently') represents a general approach to organic and peptidyl database screening. It can handle large binding-site templates and uses multi-stage indexing to identify feasible subsets of template points for ligand docking. An optimization approach based on mean-field theory is applied to model induced-fit complementarity, balancing flexibility between the ligand and the protein side chains. SLIDE can screen millions of compounds within a few days and returns a ranked list of sterically feasible ligand candidates, ranked by chemical complementarity to the protein's binding site.

See https://github.com/psa-lab to download SLIDE, and contact kuhnl@msu.edu with any questions.  Guides for using SLIDE are available to download at the end of this page.

Publications related to SLIDE include the following:

• M. I. Zavodszky, A. Rohatgi, J. R. Van Voorst, H. Yan, and L. A. Kuhn (2009) "Scoring Ligand Similarity in Structure-Based Virtual Screening" (pdf), Journal of Molecular Recognition, in press.
• L. A. Kuhn (2008) "Strength in Flexibility: Modeling Side-chain Conformational Change in Docking and Screening" (pdf), Structure-Based Drug Discovery (R. M. Stroud and J. Finer-Moore, Eds.), Royal Society of Chemistry, London, pp. 177-187.
• P. Cozzini, G. E. Kellogg, F. Spyrakis, D. J. Abraham, G. Costantino, A. Emerson, F. Fanelli, H. Gohlke, L. A. Kuhn, G. M. Morris, M. Orozco, T. A. Pertinhez, M. Rizzi, and C. A. Sotriffer (2008) "Target Flexibility: An Emerging Consideration in Drug Discovery and Design" (pdf), J. Med. Chem. 51, 6237-6255.
• M. Chubynsky, B. Hespenheide, D. J. Jacobs, L. A. Kuhn, M. Lei, S. Menor, A. J. Rader, M. F. Thorpe,W. Whiteley, and M. I. Zavodszky (2006) "Constraint Theory Applied to Proteins", in Nano-Scale Materials: From Science to Technology", (S. N. Sahu, R. K. Choudhury, and P. Jena, eds.), Nova Publishers, Hauppauge New York, pp. 77-88.
• T. A. Muller, M. I. Zavodszky, M. Feig, L. A. Kuhn, and R. P. Hausinger (2006) "Structural Basis for the Enantiomeric Specificities of R- and S-specific Phenoxypropionate/Alpha-ketoglutarate Dioxygenases" (pdf), Protein Science 15, 1356-1368.
• S. C. K. Sukuru, T. Crepin, Y. Milev, L. C. Marsh, J. B. Hill, R. J. Anderson, J. C. Morris, A. Rohatgi, G. O'Mahony, M. Grotli, F. Danel, Y. Milev, M. G. P. Page, M. Hartlein, S. Cusack, M. A. Kron, and L. A. Kuhn (2006) "Discovering New Classes of Brugia malayi Asparaginyl tRNA Synthetase Inhibitors and Relating Specificity to Conformational Change" (pdf), J. Comp.-Aided Molec. Design 20, 159-178.
• M.I. Zavodszky, L.A. Kuhn (2005) "Side-Chain Flexibility in Protein-Ligand Binding: The Minimal Rotation Hypothesis" (pdf), Protein Science, 14, 1104 - 1114.
• M. I. Zavodszky, M. Lei, A. R. Day, M. F. Thorpe, and L. A. Kuhn (2004) "Modeling Correlated Main-chain Motions in Proteins for Flexible Molecular Recognition" (pdf), Proteins: Struct. Funct. Bioinf., 57(2):243-261.
• H. Gohlke, L. A. Kuhn, and D. A. Case (2004) "Change in Protein Flexibility Upon Complex Formation: Analysis of Ras-Raf Using Molecular Dynamics and Molecular Approach" (pdf), Proteins: Struct. Funct. Bioinf., 56:322-337.
• M. I. Zavodszky, P. C. Sanschagrin, R. S. Korde, and L. A. Kuhn (2002) "Distilling the Essential Features of a Protein Surface for Improving Protein-Ligand Docking, Scoring, and Virtual Screening" (pdf), J. Comp.-Aided Molecular Design, 16, 883-902.
• E. E. Howell, U. Shukla, S. N. Hicks, R. D. Smiley, L. A. Kuhn, and M. I. Zavodszky (2001) "One Site Fits Both: A Model for the Ternary Complex of Folate + NADPH in R67 Dihydrofolate Reductase, a D2 Symmetric Enzyme" (pdf), J. Computer-Aided Molec. Design, 15, 1035-1052.
• V. Schnecke and L. A. Kuhn (2000) "Virtual Screening with Solvation and Ligand-Induced Complementarity" (pdf), Perspectives in Drug Design and Discovery, 20, 171-190.
• V. Schnecke and L. A. Kuhn (1999) "Database Screening for HIV Protease Ligands: The Influence of Binding-Site Conformation and Representation on Ligand Selectivity", Proceedings of the Seventh International Conference in Intelligent Systems for Molecular Biology, AAAI Press, pp. 242-251.
• V. Schnecke and L. A. Kuhn (1999) "Flexibly Screening for Molecules Interacting with Proteins" (pdf), in Rigidity Theory and Applications (M. F. Thorpe and P. M. Duxbury, eds.), Plenum Publishing, New York, pp. 385-400.
• V. Schnecke, C. A. Swanson, E. D. Getzoff, J. A. Tainer, and L. A. Kuhn (1998) "Screening a Peptidyl Database for Potential Ligands to Proteins with Side-chain Flexibility", Proteins: Structure, Function, and Genetics, 33, 74-87.

Please note, you will need Adobe Acrobat Reader to view the pdf files listed above. You can download a free copy of Acrobat Reader from here.

See https://github.com/psa-lab to download SLIDE. 

User Manual

SLIDE user manuals, quick guides, and tutorials:

• Quick Guide (pdf file)
• SLIDE Fact Sheet (pdf file)
• SLIDE Tutorial (pdf file)

Please note, you will need Adobe Acrobat Reader to view these pdf files. You can download a free copy of Acrobat Reader from here.

Release Notes

• SLIDE v. 3.4 Release Notes (pdf file)
• SLIDE v. 3.4 Release Notes (txt file)