MacroModel

Versatile, full-featured program for molecular modeling

The Advantages of Force Field-based Molecular Modeling

The energy and properties of a chemical system depend on the exact three-dimensional molecular structure. Subtle variations in functional groups can result in dramatic differences in behavior. Force field methods that represent the potential energy of a molecule as simple functions of distances and angles between atoms have proven to be an efficient and effective approach to obtaining accurate relative energies for chemical systems. The efficiency of force field-based calculations allows the exploration of large portions of the conformational space, revealing the detailed relationship between structure and energy.

Force field-based molecular modeling is routinely applied to examine molecular conformations, molecular motion, and intermolecular interactions for a wide range of different materials including organic and inorganic molecules and oligomers, organometallic complexes as well as complex biological systems.

Accurate energetics:
MacroModel's combination of high-quality force fields and GB/SA effective solvation model leads to reliably accurate estimations of energies.

Superior conformational analysis:
MacroModel supports a wide range of conformational searching methods, capable of handling systems ranging from small molecules to entire proteins. Investigating conformational space is important for understanding structural-property dependence, and for constructing initial models for Molecular Dynamics simulations.

Force field selection:
MacroModel supports all leading force fields, including MM2, MM3, AMBER, AMBER94, MMFF, MMFFs, OPLS, OPLS_2005 and OPLS3 , to support a wide range of research applications.

Development commitment:
Schrödinger is committed to the continued development of MacroModel. MacroModel has evolved over the years, driven by one of the largest user bases in molecular modeling, to enhance capabilities, improve performance, and to incorporate the latest scientific advances.

Citations and Acknowledgements

Schrödinger Release 2021-1: MacroModel, Schrödinger, LLC, New York, NY, 2021.

"Toward in vivo-relevant hERG safety assessment and mitigation strategies based on relationships between non-equilibrium blocker binding, three-dimensional channel-blocker interactions, dynamic occupancy, dynamic exposure, and cellular arrhythmia"

Wan, H.; Selvaggio, G.; Pearlstein, R.A., BioRxiv, 2020, Preprint, XXX-XXX

"A Comparison of Quantum and Molecular Mechanical Methods to Estimate Strain Energy in Drug-like Fragments"

Sellers, B.D.; James, N.C.; Gobbi, A., J. Chem. Inf. Model., 2017, 57 (6), 1265–1275

ö "Investigating Protein–Peptide Interactions Using the Schrödinger Computational Suite"

Bhachoo, J.; Beuming, T., Methods Mol Biol., 2017, 1561, 235-254

"Towards Understanding the Unbound State of Drug Compounds: Implications for the Intramolecular Reorganization Energy Upon Binding"

Foloppe, N.; Chen, I;, Bioorg. Med. Chem., 2016, (16), 30172-9

ö "Macrocycle Conformational Sampling with MacroModel"

Watts, K.S.; Dalal, P.; Tebben, A.J.; Cheney, D.L.; Shelley, J.C., J. Chem. Inf. Model., 2014, 54(10), 2680-2696

ö "Improved docking of polypeptides with Glide"

Tubert-Brohman, I.; Sherman, W.; Repasky, M.; Beuming, T., J. Chem. Inf. Model., 2013, 53(7), 1689-1699

"3D-QSAR using pharmacophore-based alignment and virtual screening for discovery of novel MCF-7 cell line inhibitors"

Brogi, S.; Papazafiri, P.; Roussis, V.; Tafi, A., Eur. J. Med. Chem., 2013, 67, 344-351

"Structure and absolute configuration of ginkgolide B characterized by IR- and VCD spectroscopy"

Andersen, N.H.; Lassen, P.R.; Freedman, T.B.; Nafie, L.A.; Strømgaard, K.; Hemmingsen, L., Chirality, 2010, 22, 217-223

"Molecular tweezers for enantiodiscrimination in NMR: Di-(R,R)-1-[10-(1-hydroxy-2,2,2-trifluoroethyl)-9-anthryl]-2,2,2-trifluoroethyl benzenedicarboxylates"

Gil, S.; Palomino-Schätzlein, M.; Burusco, K. K.; Jaime, C.; Virgili, A., Chirality, 2010, 22, 548–556

"1H-1,2,3-Triazol-1-yl thiodigalactoside derivatives as high affinity galectin-3 inhibitors"

Salameh, B.A.; Cumpstey, I.; Sundin, A.; Leffler, H.; Nilsson, U.J., Bioorg. Med. Chem. Lett., 2010, 18, 5367-5378

"Amide-based inhibitors of p38α MAP kinase. Part 1: Discovery of novel N-pyridyl amide lead molecules"

Luedtke, G.R.; Schinzel, K.; Tan, X.; Tester, R.W.; Nashashibi, I.; Xu, Y. et al., Bioorg. Med. Chem. Lett., 2010, 20, 2556-2559

"Effect of methyl substitution in a ligand on the selectivity and binding affinity for a nucleobase: A case study with isoxanthopterin and its derivatives"

Rajendar, B.; Rajendran, A.; Sato, Y.; Nishizawa, S.; Teramae, N., Bioorg. Med. Chem., 2009, 17, 351-359

"Differential estrogen receptor subtype modulators: Assessment of estrogen receptor subtype-binding selectivity and transcription-regulating properties of new cycloalkyl pyrazoles"

Alexi, X.; Kasiotis, K.M.; Fokialakis, N.; Lambrinidis, G.; Meligova, A.; Mikros, E. et al., J. Steroid Biochem. Mol. Biol., 2009, 117, 159-167

"Chiral discrimination processes by C9 carbamate derivatives of dihydroquinine: interaction mechanisms of diastereoisomeric 9-O-[(S)- or (R)-1-(1-naphthyl)ethylcarbamate]dihydroquinine and the two enantiomers of N-(3,5-initrobenzoyl)alanine methyl ester"

Uccello-Barretta, G.; Balzano, F.; Bardoni, S.; Vanni, L.; Giuratob, L.; Guccione, S., Tetrahedron: Asymmetry, 2008, 19, 1084–1093

"MM-GB/SA Rescoring of Docking Poses in Structure-Based Lead Optimization"

Guimarães, C. R. W.; Cardozo, M., J. Chem. Inf. Model., 2008, 48, 958–970

"A synthetic lectin analog for biomimetic disaccharide recognition"

Ferrand, Y.; Crump, M.P.; Davis, A.P., Science, 2007, 318, 619-622

"Cyclostreptin binds covalently to microtubule pores and lumenal taxoid binding sites"

Buey, R.M.; Calvo, E.; Barasoain, I.; Pineda, O.; Edler, M.C.; Matesanz, R. et al., Nat. Chem. Biol., 2007, 3, 117-125

"The site of action of oxazolidinone antibiotics in living bacteria and in human mitochondria"

Leach, K.L.; Swaney, S.M.; Colca, J.R.; McDonald, W.G.; Blinn, J.R.; Thomasco, L.M.; Gadwood, R.C.; Shinabarger, D.; Xiong, L.; Mankin, A.S., Mol. Cell., 2007, 26, 393-402

"Thyrotropin-releasing hormone and its receptors--a hypothesis for binding and receptor activation"

Engel, S.; Gershengorn, M. C., Pharmacol. Ther., 2007, 113, 410-419

"Minimum structure requirement of immunomodulatory glycolipids for predominant Th2 cytokine induction and the discovery of non-linear phytosphingosine analogs"

Toba, T.; Murata, K.; Nakanishi, K.; Takahashi, B.; Takemoto, N.; Akabane, M.; Nakatsuka, T.; Imajo, S.; Yamamura, T.; Miyake, S; Annoura, H., Bioorg. Med. Chem. Lett., 2007, 17, 2781-2784

"Identification of Residues Important for Agonist Recognition and Activation in GPR40"

Sum, C. S.; Tikhonova, I. G.; Neumann, S.; Engel, S.; Raaka, B. M.; Costanzi, S.; Gershengorn, M.C., J. Biol. Chem. , 2007, 282, 29248-29255

"Novel selective human melanocortin-3 receptor ligands: use of the 4-amino-1,2,4,5-tetrahydro-2-benzazepin-3-one (Aba) scaffold"

Ballet, S.; Mayorov, A.V.; Cai, M.; Tymecka, D.; Chandler, K.B.; Palmer, E.S.; Rompaey, K.V.; Misicka, A.; Tourwé, D.; Hruby, V.J., Bioorg. Med. Chem. Lett., 2007, 17, 2492-2498

"Synthesis, biological evaluation and molecular modeling studies of N-6-benzyladenosine analogues as potential anti-toxoplasma agents"

Kim, Y.A.; Sharon, A.; Chu, C.K.; Rais, R.H.; Al Safarjalani, O.N.; Naguib, F.N.M.; el Kouni, M.H., Biochem. Pharmacol., 2007, 73, 1558-1572

"Predicting Enantioselectivity: Computation as an Efficient "Experimental" Tool for Probing Enantioselectivity"

Ragusa, A.; Hayes, J. M.; Light, M. E.; Kilburn, J. D., Eur. J. Org. Chem., 2006, 16, 3545-3549

"Exploration of the conformational space of a polymeric material that inhibits human immunodeficiency virus"

Ercanli, T.; Boyd, D.B., J. Chem. Inf. Model., 2006, 46, 1321-1333

"Evaluation of Computational Chemistry Methods: Crystallographic and Cheminformatics Analysis of Aminothiazole Methoximes"

Ercanli, T.; Boyd, D.B., J. Chem. Inf. Model., 2005, 45, 591-601

"AMBER force field implementation of the boronate function to simulate the inhibition of beta-lactamases by alkyl and aryl boronic acids"

Tafi, A.; Agamennone, M.; Tortorella, P.; Alcaro, S.; Gallina, C.; Botta, M., Eur. J. Med. Chem., 2005, 40, 1134-1142

"Protein farnesyltransferase: Flexible docking studies on inhibitors using computational modeling"

Guida, W.C.; Hamilton, A.D.; Crotty, J.W.; Sebti, S.M., J. Comput. Aided Mol. Des., 2005, 19, 871-85

"Thermodynamic and kinetic stability of synthetic multifunctional rigid-rod beta-barrel pores: Evidence for supramolecular catalysis"

Litvinchuk, S.; Bollot, G.; Mareda, J.; Som, A.; Ronan, D.; Shah, M. R.; Perrottet, P.; Sakai, N.; Matile, S., J. Am. Chem. Soc., 2004, 126, 10067-10075

"Towards the design of host-guest complexes: biotin and urea derivatives versus artificial receptors"

Claramunt, R. M.; Herranz, F.; Santa Maria, M. D.; Jaime, C.; de Federico, M.; Elguero, J., Biosens. Bioelectron., 2004, 20, 1242-1249

"3D-QSAR and Docking Studies on 4-Anilinoquinazoline and 4-Anilinoquinoline Epidermal Growth Factor Receptor (EGFR) Tyrosine Kinase Inhibitors"

Assefa, H.; Kamath, S.; Buolamwini, J. K., J. Comput.-Aided Mol. Des., 2004, 17, 475-493

"Accurate Calculations of Ligand Binding Free Energies: Chiral Separation with Enantioselective Receptors "

Hayes, J. M.; Stein, M.; Weiser, J., J. Phys. Chem. A, 2004, 108, 3572-3580

"Biological and Conformational Study of Beta-Substituted Prolines in MT-II Template: Steric Effects Leading to Human MC5 Receptor Selectivity"

Cai, M.; Cai, C.; Mayorov, A. V.; Xiong, C.; Cabello, C. M.; Soloshonok, V. A.; Swift, J. R.; Trivedi, D.; Hruby, V. J., J. Peptide Res. , 2004, 63, 116-131

"Combining NMR and Molecular Modelling in a Drug Delivery Context: Investigation of the Multi-Mode Inclusion of a New NPY-5 Antagonist Bromobenzenesulfonamide into β-Cyclodextrin"

Uccello-Barretta, G.; Balzano, F.; Sicoli, G.; Fríglola, C.; Aldana, I.; Monge, A.; Paolino, D.; Guccione, S., Bioorg. Med. Chem., 2004, 12, 447-458

"Novel Bicyclic Sugar Modified Nucleosides: Synthesis, Conformational Analysis and Antiviral Evaluation"

Kifli, N.; Htar, T. T.; De Clercq, E.; Balzarini, J.; Simons, C., Bioorg. Med. Chem., 2004, 12, 3247-3257

"Global and local computational models for aqueous solubility prediction of drug-like molecules"

Bergstrom, C. A. S.; Wassvik, C. M.; Norinder, U.; Luthman, K.; Artursson, P., J. Chem. Inf. Comput. Sci., 2004, 44, 1477-1488

"Three-Dimensional Structure and Dynamics of Wine Tannin-Saliva Protein Complexes. A Multitechnique Approach"

Simon, C.; Barathieu, K.; Laguerre, M.; Schmitter, J.-M.; Fouquet, E.; Pianet, I.; Dufourc, E. J., Biochemistry , 2003, 42, 10385-10395

"Structure and Dynamics of the Lantibiotic Mutacin 1140"

Smith, L.; Zachariah, C.; Thirumoorthy, R.; Rocca, J.; Novak, J.; Hillman, J. D.; Edison, A. S., Biochemistry , 2003, 42, 10372-10384

"Design of Novel N-(2,4-Dioxo-1,2,3,4-tetrahydro-thieno[3,2-d]pyrimidin-7-yl)-guanidines as Thymidine Phosphorylase Inhibitors, and Flexible Docking to a Homology Model"

Price, M. L. P.; Guida, W. C.; Jackson, T. C.; Nydick, J. A.; Gladstone, P. L.; Juarez, J. C.; Doñate, F.; Ternansky, R. J., Bioorganic & Medicinal Chem. Lett. , 2003, 13, 107-110

"Molecular Descriptors Influencing Melting Point and Their Role in Classification of Solid Drugs"

Bergstrom, C. A. S.; Norinder, U.; Luthman, K.; Artursson, P., J. Chem. Inf. Comput. Sci., 2003, 43, 1177-1185

"Generation of Ligand Conformations in Continuum Solvent Consistent with Protein Active Site Topology: Application to Thromb"

Greenidge, P. A.; Mérette, S. A. M.; Beck, R.; Dodson, G.; Goodwin, C. A.; Scully, M. F.; Spencer, J.; Weiser, J.; Deadman, J. J., J. Med. Chem., 2003, 46, 1293-1305

"Toward Computing Relative Configurations: 16-epi-Latrunculin B, a New Stereoisomer of the Actin Polymerization Inhibitor Latrunculin B"

Hoye, T. R.; Ayyad, S.-E. N.; Eklov, B. M.; Hashish, N. E.; Shier, W. T.; El Sayed, K. A.; Hammann, M. T., J. Am. Chem. Soc., 2002, 124, 7405-7410

"Molecular Mechanics Calculations as Predictors of Enantioselectivity for Chiral Nucleophile Catalyzed Reactions"

Taggi, A. E.; Hafez, A. M.; Dudding, T.; Lectka, T., Tetrahedron, 2002, 58, 8351-8356

"Chemosensors for the Marine Toxin Saxitoxin"

Gawley, R. E.; Pinet, S.; Cardona, C. M.; Datta, P. K.; Ren, T.; Guida, W. C.; Nydick, J.; Leblanc, R. M., J. Am. Chem. Soc., 2002, 124, 13448-13453

"Application of the Frozen Atom Approximation to the GB/SA Continuum Model for Solvation Free Energy "

Guvench, O.; Weiser, J.; Shenkin, P.S.; Kolossváry, I.; Still, W.C., J. Comput. Chem., 2002, 23, 214-221

"Novel Agouti-Related-Protein-Based Melanocortin-1 Receptor Antagonist"

Thirumoorthy, R.; Holder, J. R.; Bauzo, R. M.; Richards, N. G. J.; Edison, A. S.; Haskell-Luevano, C., J. Med. Chem., 2001, 44, 4114-4124

"Hessian-Free Low-Mode Conformational Search for Large-Scale Protein Loop Optimization: Application to c-jun N-Terminal Kinase JNK3"

Kolossvary, I.; Keseru, G. M., J. Comp. Chem., 2001, 22, 21-30

"Fully Flexible Low-Mode Docking: Application to Induced Fit in HIV Integrase"

Keseru, G. M.; Kolossvary, I., J. Am. Chem. Soc., 2001, 123, 12708-12709

"Molecular Modeling of Bifunctional Chelate Peptide Conjugates. 1. Copper and Indium Parameters for the AMBER Force Field"

Reichert, D. E.; Norrby, P. O.; Welch, M. J., Inorg. Chem., 2001, 40, 5223-5230

"Reproducing the Conformations of Protein-bound Ligands: A Critical Evaluation of Several Popular Conformational Searching Tools"

Bostrom, J., J. Comput.-Aided Mol. Des., 2001, 15, 1137-1152

"A Comparison of Methods for Pharmacophore Generation with the Catalyst Software and their Use for 3D-QSAR: Application to a Set of 4-aminopyridine Thrombin Inhibitors"

Greenidge, P.A; Weiser, J., Mini Rev. Med. Chem., 2001, 1, 79-87

"Design, Synthesis, and Solution Structure of a Pyrrolinone-Based β-Turn Peptidomimetic"

Smith, A. B., III; Wang, W.; Sprengeler, P. A.; Hirschmann, R., J. Am. Chem. Soc., 2000, 122, 11037-11038

"Design, Synthesis and Binding Properties of Novel and Selective 5-HT3 and 5-HT4 Receptor Ligands"

Modica, M.; Santagati, M.; Guccione, S.; Russo, F.; Cagnotto, A.; Goegan, M.; Mennini, T., Eur. J. Med. Chem., 2000, 35, Erratum: ibid 2001, 36 287-301

"Stereoselective Deuterium Labeling of proRβ-protons in the NMR Structure Determination of a Helix-Turn-Helix Turn Peptidomimetic"

Etzkorn, F.A. ; Travins, J.M., J. Peptide Res., 2000, 55, 436-446

"A Self-Assembled Cylindrical Capsule: New Supramolecular Phenomena Through Encapsulation"

Korner, S. K.; Tucci, F. C.; Rudkevich, D. M.; Heinz, T.; Rebek, J., Chem. – Eur. J., 2000, 6, 187-195

"Structures of Protonated Arginine Dimer and Bradykinin Investigated by Density Functional Theory: Further Support for Stable Gas-Phase Salt Bridges "

Strittmatter, E. F.; Williams, E. R., J. Phys. Chem. A., 2000, 104, 6069-6076

"Improved Treatment of Cyclic Beta-Amino Acids and Successful Prediction of Beta-Peptide Secondary Structure using a Modified Force Field: AMBER*C"

Christianson, L. A.; Lucero, M. J.; Appella, D. H.; Klein, D. A.; Gellman, S. H., J. Comput. Chem., 2000, , 0

"The Conformations of Taxol in Chloroform"

Snyder, J. P.; Nevins, N.; Cicero, D. O.; Jansen, J., J. Am. Chem. Soc., 2000, 122, 724-725
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