The emerging role of computational design in peptide macrocycle drug discovery

References

• Lombardino JG, Lowe JA. The role of the medicinal chemist in drug discovery – then and now. Nat Rev Drug Discov. 2004;3:853–862.
   PubMed Web of Science ®Google Scholar
• Hwang TJ, Carpenter D, Lauffenburger JC, et al. Failure of investigational drugs in late-stage clinical development and publication of trial results. JAMA Intern Med. 2016;176:1826–1833.
   PubMed Web of Science ®Google Scholar
• Mullard A. 2015 FDA drug approvals. Nat Rev Drug Discov. 2016;15:73–76.
   PubMed Web of Science ®Google Scholar
• Chai CL, Mátyus P. One size does not fit all: challenging some dogmas and taboos in drug discovery. Future Med Chem. 2016;8:29–38.
   PubMed Web of Science ®Google Scholar
• Scannell JW, Blanckley A, Boldon H, et al. Diagnosing the decline in pharmaceutical R&D efficiency. Nat Rev Drug Discov. 2012;11:191–200.
   PubMed Web of Science ®Google Scholar
• Bohacek RS, McMartin C, Guida WC. The art and practice of structure-based drug design: a molecular modeling perspective. Med Res Rev. 1996;16:3–50.
   PubMed Web of Science ®Google Scholar
• Muller PY, Milton MN. The determination and interpretation of the therapeutic index in drug development. Nat Rev Drug Discov. 2012;11:751–761.
   PubMed Web of Science ®Google Scholar
• Dahlgren D, Lennernäs H. Intestinal permeability and drug absorption: predictive experimental, computational and in vivo approaches. Pharmaceutics. 2019;11.
   Web of Science ®Google Scholar
• Patel MM, Patel BM. Crossing the blood-brain barrier: recent advances in drug delivery to the brain. CNS Drugs. 2017;31:109–133.
   PubMed Web of Science ®Google Scholar
• Wang CK, Craik DJ. Cyclic peptide oral bioavailability: lessons from the past. Biopolymers. 2016;106(6):901–909.
   PubMed Web of Science ®Google Scholar
• Troeira Henriques S, Craik DJ. Cyclotide structure and function: the role of membrane binding and permeation. Biochemistry. 2017;56(5):669–682.
   PubMed Web of Science ®Google Scholar
• Ghosh AK, Gemma S. HIV-1 Protease Inhibitors for the Treatment of HIV Infection and AIDS: design of Saquinavir, Indinavir, and Darunavir. In: Ghosh AK and Gemma S, editors. Structure-Based Design of Drugs and Other Bioactive Molecules. Weinheim, Germany: Wiley-VCH Verlag GmbH & Co. KGaA; 2015. p. 237–270.
   Google Scholar
• Fettig J, Swaminathan M, Murrill CS, et al. Global epidemiology of HIV. Infectious Disease Clinics of North America. 2014;28(3):323–337.
   PubMed Web of Science ®Google Scholar
• Anderson AC. The process of structure-based drug design. Chem Biol. 2003;10(9):787–797.
   PubMed Web of Science ®Google Scholar
• Hassan Baig M, Ahmad K, Roy S, et al. Computer aided drug design: success and limitations. Current Pharmaceutical Design. 2016;22(5):572–581.
   PubMed Web of Science ®Google Scholar
• Watkins AM, Arora PS. Structure-based inhibition of protein–protein interactions. Eur J Med Chem. 2015;94:480–488.
   PubMed Web of Science ®Google Scholar
• Moiola M, Memeo MG, Quadrelli P. Stapled peptides-a useful improvement for peptide-based drugs. Molecules. 2019;24.
   Web of Science ®Google Scholar
• Rentero Rebollo I, Heinis C. Phage selection of bicyclic peptides. Methods. 2013;60(1):46–54.
   PubMed Web of Science ®Google Scholar
• Peraro L, Siegert TR, Kritzer JA. Conformational restriction of peptides using dithiol bis-alkylation. Meth Enzymol. 2016;580:303–332.
   PubMed Web of Science ®Google Scholar
• White CJ, Yudin AK. Contemporary strategies for peptide macrocyclization. Nat Chem. 2011;3(7):509–524.
   PubMed Web of Science ®Google Scholar
• Wang CK, Swedberg JE, Northfield SE, et al. Effects of cyclization on peptide backbone dynamics. J Phys Chem B. 2015;119(52):15821–15830.
   PubMed Web of Science ®Google Scholar
• Est CB, Mangrolia P, Murphy RM. ROSETTA-informed design of structurally stabilized cyclic anti-amyloid peptides. Protein Eng Des Sel. 2019;gzz016. DOI:10.1093/protein/gzz016.
   Web of Science ®Google Scholar
• Bhardwaj G, Mulligan VK, Bahl CD, et al., Accurate de novo design of hyperstable constrained peptides. Nature. 2016;538(7625):329–335.
   PubMed Web of Science ®Google Scholar
• Hosseinzadeh P, Bhardwaj G, Mulligan VK, et al., Comprehensive computational design of ordered peptide macrocycles. Science. 2017;358(6369):1461–1466.
   PubMed Web of Science ®Google Scholar
• Dang B, Wu H, Mulligan VK, et al. De novo design of covalently constrained mesosize protein scaffolds with unique tertiary structures. Proceedings of the National Academy of Sciences. 2017;114:10852–10857.
   Google Scholar
• Wishart DS, Knox C, Guo AC, et al. DrugBank: a comprehensive resource for in silico drug discovery and exploration. Nucleic Acids Res. 2006;34(90001):D668–672.
   PubMedGoogle Scholar
• Wishart DS, Feunang YD, Guo AC, et al. DrugBank 5.0: a major update to the DrugBank database for 2018. Nucleic Acids Res. 2018;46(D1):D1074–D1082.
   PubMed Web of Science ®Google Scholar
• Lipinski CA, Lombardo F, Dominy BW, et al. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings 1PII of original article: S0169-409X(96)00423-1. The article was originally published in Advanced Drug Delivery Reviews 23 (1997) 3–25. 1. Advanced Drug Delivery Reviews. 2001;46(1–3):3–26.
   PubMed Web of Science ®Google Scholar
• Craik DJ, Fairlie DP, Liras S, et al. The future of peptide-based drugs. Chem Biol Drug Des. 2013;81(1):136–147.
   PubMed Web of Science ®Google Scholar
• Jia L, Zhang L, Shao C, et al. An attempt to understand kidney’s protein handling function by comparing plasma and urine proteomes. PLoS ONE. 2009;4(4):e5146.
   PubMed Web of Science ®Google Scholar
• Chirmule N, Jawa V, Meibohm B. Immunogenicity to therapeutic proteins: impact on PK/PD and efficacy. Aaps J. 2012;14(2):296–302.
   PubMed Web of Science ®Google Scholar
• Hollstein U, Breitmaier E, Jung G. Carbon-13 nuclear magnetic resonance study of actinomycin D. J Am Chem Soc. 1974;96(26):8036–8040.
   PubMed Web of Science ®Google Scholar
• Hotchkiss RD, Dubos RJ. Bactericidal fractions from an aerobic sporulating bacillus. J Biol Chem. 1940;136:803–804.
   Google Scholar
• Johnson BA, Anker H, Meleney FL. Bacitracin: A new antibiotic produced by a member of the B. subtilis group. Science. 1945;102:376–377.
   PubMed Web of Science ®Google Scholar
• Benedict RG, Langlykke AF. Antibiotic activity of Bacillus polymyxa. J Bacteriol. 1947;54:24.
   PubMed Web of Science ®Google Scholar
• Koyama Y. A new antibiotic “colistin” produced by spore-forming soil bacteria. J Antibiot. 1950;3:457–458.
   Google Scholar
• Ehrlich J, Smith RM, Penner MA, et al. Antimicrobial activity of streptomyces floridae and of viomycin. Am Rev Tuberc. 1951;63(1):7–16.
   PubMedGoogle Scholar
• Finlay AC, Hobby GL, Hoschstein F, et al. Viomycin a new antibiotic active against mycobacteria. Am Rev Tuberc. 1951;63(1):1–3.
   PubMedGoogle Scholar
• Herr EB Jr, Haney ME, Pittenger GE. Capreomycin: A new peptide antibiotic. Am Chem Soc. 1961;Abstract 49C. 140th Meeting.
   Web of Science ®Google Scholar
• Jolles G, Terlain B, Thomas JP. Metabolic investigations on pristinamycin. Nature. 1965;207(4993):199–200.
   PubMed Web of Science ®Google Scholar
• Heusler K, Pletscher A. The controversial early history of cyclosporin.. Swiss Med Wkly. 2001;131(21–22):299–302.
   PubMed Web of Science ®Google Scholar
• Bauer W, Briner U, Doepfner W, et al., SMS 201–995: A very potent and selective octapeptide analogue of somatostatin with prolonged action. Life Sci. 1982;31(11):1133–1140.
   PubMed Web of Science ®Google Scholar
• Eliopoulos GM, Willey S, Reiszner E, et al. In vitro and in vivo activity of LY 146032, a new cyclic lipopeptide antibiotic. Antimicrobial Agents and Chemotherapy. 1986;30(4):532–535.
   PubMed Web of Science ®Google Scholar
• Fass RJ, Helsel VL. In vitro activity of LY146032 against staphylococci, streptococci, and enterococci.. Antimicrobial Agents and Chemotherapy. 1986;30(5):781–784.
   PubMed Web of Science ®Google Scholar
• Knapp CC, Washington JA. Antistaphylococcal activity of a cyclic peptide, LY146032, and vancomycin. Antimicrobial Agents and Chemotherapy. 1986;30(6):938–939.
   PubMed Web of Science ®Google Scholar
• Adrian HJ, Dörr U, Bach D, et al. Biodistribution of 111In-pentetreotide and dosimetric considerations with respect to somatostatin receptor expressing tumor burden. Hormone and Metabolic Research. Supplement Series. 1993;27:18–23.
   PubMedGoogle Scholar
• Joseph K, Stapp J, Reinecke J, et al. Receptor scintigraphy with 111In-pentetreotide for endocrine gastroenteropancreatic tumors. Hormone and Metabolic Research. Supplement Series. 1993;27:28–35.
   PubMedGoogle Scholar
• Dörr U, Räth U, Sautter-Bihl M-L, et al. Improved visualization of carcinoid liver metastases by indium-111 pentetreotide scintigraphy following treatment with cold somatostatin analogue. Eur J Nucl Med. 1993;20(5):431–433.
   PubMedGoogle Scholar
• Ernst ME, Klepser ME, Wolfe EJ, et al. Antifungal dynamics of LY 303366, an investigational echinocandin B analog, against Candida ssp. Diagnostic Microbiology and Infectious Disease. 1996;26(3–4):125–131.
   PubMed Web of Science ®Google Scholar
• Bartlett MS, Current WL, Goheen MP, et al. Semisynthetic echinocandins affect cell wall deposition of Pneumocystis carinii in vitro and in vivo. Antimicrobial Agents and Chemotherapy. 1996;40(8):1811–1816.
   PubMed Web of Science ®Google Scholar
• Del Poeta M, Schell WA, Perfect JR. In vitro antifungal activity of pneumocandin L-743,872 against a variety of clinically important molds. Antimicrobial Agents and Chemotherapy. 1997;41(8):1835–1836.
   PubMed Web of Science ®Google Scholar
• Vazquez JA, Lynch M, Boikov D, et al. In vitro activity of a new pneumocandin antifungal, L-743,872, against azole-susceptible and -resistant Candida species. Antimicrobial Agents and Chemotherapy. 1997;41(7):1612–1614.
   PubMed Web of Science ®Google Scholar
• Scarborough RM, Naughton MA, Teng W, et al. Design of potent and specific integrin antagonists. peptide antagonists with high specificity for glycoprotein IIb-IIIa. The Journal of Biological Chemistry. 1993;268(2):1066–1073.
   PubMed Web of Science ®Google Scholar
• Ueda H, Nakajima H, Hori Y, et al. FR901228, a novel antitumor bicyclic depsipeptide produced by chromobacterium violaceum No. 968. I. Taxonomy, fermentation, isolation, physico-chemical and biological properties, and antitumor activity. The Journal of Antibiotics. 1994;47(3):301–310.
   PubMed Web of Science ®Google Scholar
• Tawara S, Ikeda F, Maki K, et al. In vitro activities of a new lipopeptide antifungal agent, FK463, against a variety of clinically important fungi. Antimicrob Agents Chemother. 2000;44(1):57–62.
   PubMed Web of Science ®Google Scholar
• Kwekkeboom DJ, Teunissen JJ, Bakker WH, et al. Radiolabeled somatostatin analog [177 Lu-DOTA 0,Tyr 3]Octreotate in patients with endocrine gastroenteropancreatic Tumors. JCO. 2005;23(12):2754–2762.
   PubMed Web of Science ®Google Scholar
• Decristoforo C, Knopp R, von Guggenberg E, et al. A fully automated synthesis for the preparation of 68Ga-labelled peptides. Nucl Med Commun. 2007;28(11):870–875.
   PubMed Web of Science ®Google Scholar
• Win Z, Rahman L, Murrell J, et al. The possible role of 68Ga-DOTATATE PET in malignant abdominal paraganglioma. European Journal of Nuclear Medicine and Molecular Imaging. 2006;33(4):506.
   PubMed Web of Science ®Google Scholar
• Win Z, Al-Nahhas A, Towey D, et al. 68Ga-DOTATATE PET in neuroectodermal tumours: first experience. Nucl Med Commun. 2007;28(5):359–363.
   PubMed Web of Science ®Google Scholar
• World health organization model list of essential medicines, 21st list [Internet]. World Health Organization; 2019 [ cited 2019 Dec 16]. Available from: https://apps.who.int/iris/bitstream/handle/10665/325771/WHO-MVP-EMP-IAU-2019.06-eng.pdf.
   Google Scholar
• Yu X, Sun D. Macrocyclic drugs and synthetic methodologies toward macrocycles. Molecules. 2013;18(6):6230–6268.
   PubMed Web of Science ®Google Scholar
• Kumar R, Feltrup TM, Kukreja RV, et al. Evolutionary features in the structure and function of bacterial toxins. Toxins (Basel). 2019;11(1):15.
   Web of Science ®Google Scholar
• Peigneur S, Tytgat J. Toxins in drug discovery and pharmacology. Toxins (Basel). 2018;10.
   Web of Science ®Google Scholar
• May JP, Perrin DM. Tryptathionine bridges in peptide synthesis. Biopolymers. 2007;88(5):714–724.
   PubMed Web of Science ®Google Scholar
• Mir R, Karim S, Kamal MA, et al. Conotoxins: structure, therapeutic potential and pharmacological applications. Current Pharmaceutical Design. 2016;22(5):582–589.
   PubMed Web of Science ®Google Scholar
• Clark RJ, Fischer H, Dempster L, et al. Engineering stable peptide toxins by means of backbone cyclization: stabilization of the -conotoxin MII. Proceedings of the National Academy of Sciences 2005;102(39):13767–13772.
   PubMed Web of Science ®Google Scholar
• Conibear AC, Craik DJ. The chemistry and biology of theta defensins. Angewandte Chemie International Edition. 2014;53(40):10612–10623.
   PubMed Web of Science ®Google Scholar
• Akondi KB, Muttenthaler M, Dutertre S, et al. Discovery, synthesis, and structure–activity relationships of conotoxins. Chemical Reviews. 2014;114(11):5815–5847.
   PubMed Web of Science ®Google Scholar
• Ireland DC, Colgrave ML, Craik DJ. A novel suite of cyclotides from viola odorata: sequence variation and the implications for structure, function and stability. Biochem J. 2006;400(1):1–12.
   PubMedGoogle Scholar
• Kohli RM, Walsh CT. Enzymology of acyl chain macrocyclization in natural product biosynthesis. Chemical Communications. 2003;3:297–307. DOI:10.1039/b208333g
   PubMed Web of Science ®Google Scholar
• Bouaïcha N, Miles CO, Beach DG, et al. Structural diversity, characterization and toxicology of microcystins. Toxins (Basel). 2019;11(12):714.
   Web of Science ®Google Scholar
• Behrendt R, White P, Offer J. Advances in Fmoc solid-phase peptide synthesis. Journal of Peptide Science. 2016;22(1):4–27.
   PubMed Web of Science ®Google Scholar
• Mäde V, Els-Heindl S, Beck-Sickinger AG. Automated solid-phase peptide synthesis to obtain therapeutic peptides. Beilstein J Org Chem. 2014;10:1197–1212.
   PubMed Web of Science ®Google Scholar
• Weinstock MT, Francis JN, Redman JS, et al. Protease-resistant peptide design-empowering nature’s fragile warriors against HIV. Biopolymers. 2012;98(5):431–442.
   PubMed Web of Science ®Google Scholar
• Dintzis HM, Symer DE, Dintzis RZ, et al. A comparison of the immunogenicity of a pair of enantiomeric proteins. Proteins: Structure, Function, and Genetics. 1993;16(3):306–308.
   PubMed Web of Science ®Google Scholar
• Ashby M, Petkova A, Gani J, et al. Use of peptide libraries for identification and optimization of novel antimicrobial peptides. Curr Top Med Chem. 2016;17(5):537–553.
   Web of Science ®Google Scholar
• Passioura T, Katoh T, Goto Y, et al. Selection-based discovery of druglike macrocyclic peptides. Annual Review of Biochemistry. 2014;83(1):727–752.
   PubMedGoogle Scholar
• Zaretsky S, Tan J, Hickey JL, et al. Macrocyclic templates for library synthesis of peptido-conjugates. Methods Mol Biol. 2015;1248:67–80.
   PubMedGoogle Scholar
• Pellois JP, Zhou X, Srivannavit O, et al. Individually addressable parallel peptide synthesis on microchips. Nat Biotechnol. 2002;20(9):922–926.
   PubMed Web of Science ®Google Scholar
• Playe B, Azencott C-A, Stoven V. Efficient multi-task chemogenomics for drug specificity prediction. Plos One. 2018;13(10):e0204999.
   PubMed Web of Science ®Google Scholar
• Yan Z, Wang J. Specificity quantification of biomolecular recognition and its implication for drug discovery. Sci Rep. 2012;2(1):309.
   PubMedGoogle Scholar
• Boothroyd S, Kerridge A, Broo A, et al. Solubility prediction from first principles: a density of states approach. Phys Chem Chem Phys. 2018;20(32):20981–20987.
   PubMed Web of Science ®Google Scholar
• Bergström CAS, Larsson P. Computational prediction of drug solubility in water-based systems: qualitative and quantitative approaches used in the current drug discovery and development setting. Int J Pharm. 2018;540(1–2):185–193.
   PubMed Web of Science ®Google Scholar
• Egan WJ, Lauri G. Prediction of intestinal permeability. Advanced Drug Delivery Reviews. 2002;54(3):273–289.
   PubMed Web of Science ®Google Scholar
• Dickson CJ, Hornak V, Pearlstein RA, et al. Structure–kinetic relationships of passive membrane permeation from multiscale modeling. Journal of the American Chemical Society. 2017;139(1):442–452.
   PubMed Web of Science ®Google Scholar
• Zhang L, Zhang H, Ai H, et al. Applications of machine learning methods in drug toxicity prediction. Curr Top Med Chem. 2018;18(12):987–997.
   PubMed Web of Science ®Google Scholar
• Li X, Chen L, Cheng F, et al., In silico prediction of chemical acute oral toxicity using multi-classification methods. J Chem Inf Model. 2014;54(4):1061–1069.
   PubMed Web of Science ®Google Scholar
• Shaw DE, Maragakis P, Lindorff-Larsen K, et al., Atomic-level characterization of the structural dynamics of proteins. Science. 2010;330(6002):341–346.
   PubMed Web of Science ®Google Scholar
• Hwang H, Schatz G, Ratner M. coarse-grained molecular dynamics study of cyclic peptide nanotube insertion into a lipid bilayer†. J Phys Chem A. 2009;113(16):4780–4787.
   PubMed Web of Science ®Google Scholar
• Kuhlman B, Dantas G, Ireton GC, et al., Design of a novel globular protein fold with atomic-level accuracy. Science. 2003;302(5649):1364–1368.
   PubMed Web of Science ®Google Scholar
• Appella DH, Christianson LA, Klein DA, et al. Residue-based control of helix shape in β-peptide oligomers. Nature. 1997;387(6631):381–384.
   PubMed Web of Science ®Google Scholar
• Giuliano MW, Horne WS, Gellman SH. An α/β-Peptide helix bundle with a pure β3 -amino acid core and a distinctive quaternary structure. Journal of the American Chemical Society. 2009;131(29):9860–9861.
   PubMed Web of Science ®Google Scholar
• Horne WS, Gellman SH. Foldamers with Heterogeneous Backbones. Acc Chem Res. 2008;41(10):1399–1408.
   PubMed Web of Science ®Google Scholar
• Slough DP, McHugh SM, Cummings AE, et al. Designing well-structured cyclic pentapeptides based on sequence–structure relationships. J Phys Chem B. 2018;122(14):3908–3919.
   PubMed Web of Science ®Google Scholar
• Kritzer JA, Hodsdon ME, Schepartz A. Solution structure of a β-Peptide ligand for hDM2. Journal of the American Chemical Society. 2005;127(12):4118–4119.
   PubMed Web of Science ®Google Scholar
• Burley SK, Berman HM, Bhikadiya C, et al. RCSB protein data bank: biological macromolecular structures enabling research and education in fundamental biology, biomedicine, biotechnology and energy. Nucleic Acids Res. 2019;47(D1):D464–D474.
   PubMed Web of Science ®Google Scholar
• Handl J, Knowles J, Vernon R, et al. The dual role of fragments in fragment-assembly methods for de novo protein structure prediction. Proteins: Structure, Function, and Bioinformatics. 2012;80(2):490–504.
   PubMed Web of Science ®Google Scholar
• Simons KT, Bonneau R, Ruczinski I, et al. Ab initio protein structure prediction of CASP III targets using ROSETTA. Proteins. 1999;Suppl 3:171–176.
   PubMedGoogle Scholar
• King CA, Bradley P. Structure-based prediction of protein-peptide specificity in Rosetta. Proteins: Structure, Function, and Bioinformatics. 2010;78(16):3437–3449.
   PubMed Web of Science ®Google Scholar
• Raveh B, London N, Schueler-Furman O. Sub-angstrom modeling of complexes between flexible peptides and globular proteins. Proteins. 2010;78(9):2029–2040.
   PubMed Web of Science ®Google Scholar
• London N, Raveh B, Schueler-Furman O. Peptide docking and structure-based characterization of peptide binding: from knowledge to know-how. Current Opinion in Structural Biology. 2013;23(6):894–902.
   PubMed Web of Science ®Google Scholar
• Coutsias EA, Seok C, Jacobson MP, et al. A kinematic view of loop closure. J Comput Chem. 2004;25(4):510–528.
   PubMed Web of Science ®Google Scholar
• Mandell DJ, Coutsias EA, Kortemme T. Sub-angstrom accuracy in protein loop reconstruction by robotics-inspired conformational sampling. Nature Methods. 2009;6(8):551–552.
   PubMed Web of Science ®Google Scholar
• Mulligan VK Generalized kinematic closure (GeneralizedKIC) tutorial series [Internet]. 2017 [ cited 2019 Nov 14]. Available from: https://www.rosettacommons.org/demos/latest/tutorials/GeneralizedKIC/generalized_kinematic_closure_1.
   Google Scholar
• Sindhikara D, Spronk SA, Day T, et al. Improving accuracy, diversity, and speed with prime macrocycle conformational sampling. Journal of Chemical Information and Modeling. 2017;57(8):1881–1894.
   PubMed Web of Science ®Google Scholar
• Sindhikara D, Borrelli K. High throughput evaluation of macrocyclization strategies for conformer stabilization. Sci Rep. 2018;8(1):6585.
   PubMedGoogle Scholar
• Renfrew PD, Choi EJ, Bonneau R, et al., Incorporation of noncanonical amino acids into rosetta and use in computational protein-peptide interface design. Uversky VN, editor. PLoS One. 2012;7(3):e32637.
   PubMed Web of Science ®Google Scholar
• Alford RF, Leaver-Fay A, Jeliazkov JR, et al. The rosetta all-atom energy function for macromolecular modeling and design. J Chem Theory Comput. 2017;13(6):3031–3048.
   PubMed Web of Science ®Google Scholar
• Park H, Bradley P, Greisen P, et al. Simultaneous optimization of biomolecular energy functions on features from small molecules and macromolecules. J Chem Theory Comput. 2016;12(12):6201–6212.
   PubMed Web of Science ®Google Scholar
• Dunbrack RL, Karplus M. Backbone-dependent rotamer library for proteins application to side-chain prediction. Journal of Molecular Biology. 1993;230(2):543–574.
   PubMed Web of Science ®Google Scholar
• Shapovalov MV, Dunbrack RL. A smoothed backbone-dependent rotamer library for proteins derived from adaptive kernel density estimates and regressions. Structure. 2011;19(6):844–858.
   PubMed Web of Science ®Google Scholar
• Mironov V, Alexeev Y, Mulligan VK, et al. A systematic study of minima in alanine dipeptide. J Comput Chem. 2019;40(2):297–309.
   PubMed Web of Science ®Google Scholar
• Renfrew PD, Butterfoss GL, Kuhlman B. Using quantum mechanics to improve estimates of amino acid side chain rotamer energies. Proteins: Structure, Function, and Bioinformatics. 2007;71(4):1637–1646.
   Web of Science ®Google Scholar
• Vanhee P, van der Sloot AM, Verschueren E, et al. Computational design of peptide ligands. Trends Biotechnol. 2011;29(5):231–239.
   PubMed Web of Science ®Google Scholar
• Wang J, Cao H, Zhang JZH, et al. computational protein design with deep learning neural networks. Sci Rep. 2018;8(1):6349.
   PubMedGoogle Scholar
• Traoré S, Allouche D, André I, et al. A new framework for computational protein design through cost function network optimization. Bioinformatics. 2013;29(17):2129–2136.
   PubMed Web of Science ®Google Scholar
• Hallen MA, Martin JW, Ojewole A, et al., OSPREY 3.0: open-source protein redesign for you, with powerful new features. J Comput Chem. 2018;39(30):2494–2507.
   PubMed Web of Science ®Google Scholar
• Leaver-Fay A, Tyka M, Lewis SM, et al. Rosetta3. In: Johnson ML and Brand L, editors. Methods in Enzymology. San Deigo (CA): Elsevier; 2011. p. 545–574.
   Google Scholar
• Mulligan VK Design-centric guidance terms [Internet]. 2017 [ cited 2019 Dec 12]. Available from: https://www.rosettacommons.org/docs/latest/rosetta_basics/scoring/design-guidance-terms.
   Google Scholar
• Loosli H-R, Kessler H, Oschkinat H, et al. Peptide conformations. Part 31. The conformation of cyclosporin A in the crystal and in solution. Helvetica Chimica Acta. 1985;68(3):682–704.
   Web of Science ®Google Scholar
• Witek J, Keller BG, Blatter M, et al. Kinetic models of cyclosporin a in polar and apolar environments reveal multiple congruent conformational states. J Chem Inf Model. 2016;56:1547–1562.
   PubMed Web of Science ®Google Scholar
• Fleishman SJ, Leaver-Fay A, Corn JE, et al. RosettaScripts: a scripting language interface to the Rosetta macromolecular modeling suite. PLoS ONE. 2011;6:e20161.
   PubMed Web of Science ®Google Scholar
• Chaudhury S, Lyskov S, Gray JJ. PyRosetta: a script-based interface for implementing molecular modeling algorithms using Rosetta. Bioinformatics. 2010;26:689–691.
   PubMed Web of Science ®Google Scholar
• Mulligan VK Simple cyclic peptide prediction (simple_cycpep_predict) application [internet]. 2015 [ cited 2019 Nov 18]. Available from: https://www.rosettacommons.org/docs/latest/structure_prediction/simple_cycpep_predict.
   Google Scholar
• Fesik SW, Gampe RT, Eaton HL, et al. NMR studies of [U-13C]cyclosporin A bound to cyclophilin: bound conformation and portions of cyclosporin involved in binding. Biochemistry. 1991;30:6574–6583.
   PubMed Web of Science ®Google Scholar
• Stegmann CM, Seeliger D, Sheldrick GM, et al. The thermodynamic influence of trapped water molecules on a protein-ligand interaction. Angew Chem Int Ed Engl. 2009;48:5207–5210.
   PubMed Web of Science ®Google Scholar
• El Tayar N, Mark AE, Vallat P, et al. Solvent-dependent conformation and hydrogen-bonding capacity of cyclosporin A: evidence from partition coefficients and molecular dynamics simulations. J Med Chem. 1993;36:3757–3764.
   PubMed Web of Science ®Google Scholar
• Peraro L, Kritzer JA. Emerging methods and design principles for cell-penetrant peptides. Angew Chem Int Ed Engl. 2018;57:11868–11881.
   PubMed Web of Science ®Google Scholar
• Rossi Sebastiano M, Doak BC, Backlund M, et al. Impact of dynamically exposed polarity on permeability and solubility of chameleonic drugs beyond the rule of 5. J Med Chem. 2018;61:4189–4202.
   PubMed Web of Science ®Google Scholar
• Wang CK, Swedberg JE, Harvey PJ, et al. Conformational Flexibility Is a Determinant of Permeability for Cyclosporin. J Phys Chem B. 2018;122:2261–2276.
   PubMed Web of Science ®Google Scholar
• Danelius E, Poongavanam V, Peintner S, et al. Solution conformations explain the chameleonic behaviour of macrocyclic drugs. Chem Eur J. 2020;chem.201905599.
   PubMed Web of Science ®Google Scholar
• Matsson P, Kihlberg J. How big is too big for cell permeability? J. Med Chem. 2017;60:1662–1664.
   Web of Science ®Google Scholar
• Pye CR, Hewitt WM, Schwochert J, et al. nonclassical size dependence of permeation defines bounds for passive adsorption of large drug molecules. J Med Chem. 2017;60:1665–1672.
   PubMed Web of Science ®Google Scholar
• Over B, Matsson P, Tyrchan C, et al. Structural and conformational determinants of macrocycle cell permeability. Nat Chem Biol. 2016;12:1065–1074.
   PubMed Web of Science ®Google Scholar
• Alford RF, Koehler Leman J, Weitzner BD, et al. An integrated framework advancing membrane protein modeling and design. PLoS Comput Biol. 2015;11:e1004398.
   PubMed Web of Science ®Google Scholar
• Lu P, Min D, DiMaio F, et al. Accurate computational design of multipass transmembrane proteins. Science. 2018;359:1042–1046.
   PubMed Web of Science ®Google Scholar
• Butterfoss GL, Renfrew PD, Kuhlman B, et al. a preliminary survey of the peptoid folding landscape. J Am Chem Soc. 2009;131:16798–16807.
   PubMed Web of Science ®Google Scholar
• Butterfoss GL, Drew K, Renfrew PD, et al. Conformational preferences of peptide-peptoid hybrid oligomers: conformational preferences of peptide-peptoid oligomers. Biopolymers. 2014;102:369–378.
   PubMed Web of Science ®Google Scholar
• Lewis SM Release Notes – rosetta 3.11 [Internet]. Rosetta Commons; 2019 [ cited 2019 Dec 15]. Available from: https://www.rosettacommons.org/docs/latest/Release-Notes#rosetta-3-11.
   Google Scholar
• Drew K, Renfrew PD, Craven TW, et al. Adding diverse noncanonical backbones to rosetta: enabling peptidomimetic design. Uversky VN, editor. PLoS One. 2013;8:e67051.
   PubMed Web of Science ®Google Scholar
• Leaver-Fay A, Jacak R, Stranges PB, et al. a generic program for multistate protein design. Plos One. 2011;6:e20937.
   PubMed Web of Science ®Google Scholar
• Huang J, Rauscher S, Nawrocki G, et al. CHARMM36m: an improved force field for folded and intrinsically disordered proteins. Nat Methods. 2017;14:71–73.
   PubMed Web of Science ®Google Scholar
• Maier JA, Martinez C, Kasavajhala K, et al. FF14SB: improving the accuracy of protein side chain and backbone parameters from FF99SB. J Chem Theory Comput. 2015;11:3696–3713.
   PubMed Web of Science ®Google Scholar
• Case DA, Cheatham TE, Darden T, et al. The Amber biomolecular simulation programs. J Comput Chem. 2005;26:1668–1688.
   PubMed Web of Science ®Google Scholar
• Alexeev Y, Mazanetz MP, Ichihara O, et al. GAMESS as a free quantum-mechanical platform for drug research. Curr Top Med Chem. 2012;12:2013–2033.
   PubMed Web of Science ®Google Scholar
• Parrish RM, Burns LA, Smith DGA, et al. Psi4 1.1: an open-source electronic structure program emphasizing automation, advanced libraries, and interoperability. J Chem Theory Comput. 2017;13:3185–3197.
   PubMed Web of Science ®Google Scholar
• Valiev M, Bylaska EJ, Govind N, et al. NWChem: A comprehensive and scalable open-source solution for large scale molecular simulations. Comput Phys Commun. 2010;181:1477–1489.
   Web of Science ®Google Scholar
• Fedorov DG, Brekhov A, Mironov V, et al. molecular electrostatic potential and electron density of large systems in solution computed with the fragment molecular orbital method. J Phys Chem A. 2019;123:6281–6290.
   PubMed Web of Science ®Google Scholar
• Dill KA, Chan HS. From Levinthal to pathways to funnels. Nat Struct Biol. 1997;4:10.
   PubMedGoogle Scholar
• Lazaridis T, Karplus M. Discrimination of the native from misfolded protein models with an energy function including implicit solvation. J Mol Biol. 1999;288 Fersht AR 11Edited by. 477–487.
   PubMed Web of Science ®Google Scholar
• He S, Li Y, Feng Y, et al. Learning to predict the cosmological structure formation. PNAS. 2019;116:13825–13832.
   PubMed Web of Science ®Google Scholar
• Bauer BA, Davis JE, Taufer M, et al. Molecular dynamics simulations of aqueous ions at the liquid-vapor interface accelerated using graphics processors. J Comput Chem. 2011;32:375–385.
   PubMed Web of Science ®Google Scholar
• Mermelstein DJ, Lin C, Nelson G, et al. Fast and flexible GPU accelerated binding free energy calculations within the amber molecular dynamics package. J Comput Chem. 2018;39:1354–1358.
   PubMed Web of Science ®Google Scholar
• Fernandes KD, Renison CA, Naidoo KJ. Quantum supercharger library: hyper-parallelism of the Hartree-Fock method. J Comput Chem. 2015;36:1399–1409.
   PubMed Web of Science ®Google Scholar
• Wilkinson KA, Sherwood P, Guest MF, et al. Acceleration of the GAMESS-UK electronic structure package on graphical processing units. J Comput Chem. 2011;32:2313–2318.
   PubMed Web of Science ®Google Scholar
• Chiu M, Herbordt MC. molecular dynamics simulations on high-performance reconfigurable computing systems. 2010;3. ACM Trans Reconfigurable Technol Syst.
   Web of Science ®Google Scholar
• Feynman RP. Simulating physics with computers. Int J Theor Phys. 1982;21:467–488.
   Web of Science ®Google Scholar
• Preskill J. Quantum Computing in the NISQ era and beyond. Quantum. 2018;2:79.
   Web of Science ®Google Scholar
• Babej T, Ing C,Fingerhuth M. Coarse-grained lattice protein folding on a quantum annealer. arXiv:1811.00713 [quant-ph] [ Internet]. 2018 [ cited 2019 Dec 12]; Available from: http://arxiv.org/abs/1811.00713.
   Google Scholar
• Mulligan VK, Melo H, Merritt HI, et al. Designing peptides on a quantum computer. bioRxiv. 2019;752485.
   Google Scholar
• RosettaCommons website [Internet]. [ cited 2019 Dec 12]. Available from: https://www.rosettacommons.org/.
   Google Scholar
• Donald B. Osprey 3.0, donald lab at duke university [internet]. [cited 2019 Dec 13]. Available from: https://www2.cs.duke.edu/donaldlab/osprey.php.
   Google Scholar
• de Givry S Toulbar2: an exact solver for cost function networks [Internet]. [cited 2019 Dec 13]. Available from: https://miat.inrae.fr/toulbar2/.
   Google Scholar
• CHARMM Registration [Internet]. [ cited 2020 Mar 21]. Available from: http://charmm.chemistry.harvard.edu/.
   Google Scholar
• Download Amber MD [Internet]. [ cited 2020 Mar 21]. Available from: https://ambermd.org/GetAmber.php.
   Google Scholar
• Gordon Group/GAMESS Homepage [Internet]. [ cited 2020 Mar 21]. Available from: https://www.msg.chem.iastate.edu/gamess/index.html.
   Google Scholar
• Psi4: Open-source quantum chemistry [internet]. [ cited 2020 Mar 21]. Available from: http://www.psicode.org/.
   Google Scholar
• NWChem: open source high-performance computational chemistry [internet]. [ cited 2020 Mar 21]. Available from: http://www.nwchem-sw.org/index.php/Main_Page.
   Google Scholar