4,453
Views
3
CrossRef citations to date
0
Altmetric
Review

The emerging potential of interactive virtual reality in drug discovery

ORCID Icon, , , &
Pages 685-698 | Received 09 Feb 2022, Accepted 16 May 2022, Published online: 02 Jun 2022

References

  • Gund P, Andose JD, Rhodes JB, et al. Three-dimensional molecular modeling and drug design. Science. 1980;208(4451):1425–1431.
  • Marshall GR. Computer-aided drug design. Annu Rev Pharmacol Toxicol. 1987;27(1):193–213.
  • Van Drie JH. Computer-aided drug design: the next 20 years. J Comput Aided Mol Des. 2007;21(10):591–601.
  • Macalino SJY, Gosu V, Hong S, et al. Role of computer-aided drug design in modern drug discovery. Arch Pharm Res. 2015;38(9):1686–1701.
  • Jorgensen WL. The many roles of computation in drug discovery. Science. 2004;303(5665):1813–1818.
  • Lovering F, Bikker J, Humblet C. Escape from flatland: increasing saturation as an approach to improving clinical success. J Med Chem. 2009;52(21):6752–6756.
  • Lovering F. Escape from Flatland 2: complexity and promiscuity. Med Chem Comm. 2013;4(3):515–519.
  • Licklider JC. Man-computer symbiosis. IRE Trans Human Factors Electron. 1960;1:4–11.
  • Wright WG. Using virtual reality to augment perception, enhance sensorimotor adaptation, and change our minds. Front Syst Neurosci. 2014;8:56.
  • Biocca F, Delaney B. Immersive virtual reality technology. Communication in the Age of Virtual Reality. 1995;15(32):10–5555.
  • Sutherland IE, editor. A head-mounted three dimensional display. Proceedings of the December 9-11, 1968, Fall Joint Computer Conference, Part I, San Francisco, California; 1968.
  • Krueger MW, Gionfriddo T, Hinrichsen K, editors. VIDEOPLACE—an artificial reality. Proceedings of the SIGCHI Conference on Human Factors in Computing Systems, San Francisco, California; 1985.
  • Lanier J. Virtual reality: the promise of the future. Interact Learn Int. 1992;8(4):275–279.
  • Fisher SS, McGreevy M, Humphries J, et al., editors. Virtual environment display system. Proceedings of the 1986 workshop on Interactive 3D graphics, Chapel Hill, North Carolina USA; 1987.
  • Lippman A. Movie-maps: an application of the optical videodisc to computer graphics. Acm Siggraph Comput Graphics. 1980;14(3):32–42.
  • Sutherland I. The ultimate display. 1965
  • Shakya S. Virtual restoration of damaged archeological artifacts obtained from expeditions using 3D visualization. J Innovative Image Process (JIIP). 2019;1(2):102–110.
  • Lütjens M, Kersten TP, Dorschel B, et al. Virtual reality in cartography: immersive 3D visualization of the arctic clyde inlet (Canada) using digital elevation models and bathymetric data. Multimodal Technol Inter. 2019;3(1):9.
  • Li R. Dynamic three-dimensional visualization system of sea area flow field based on virtual reality technology. Ccamlr Sci. 2019;26(1):23–29.
  • Poyade M, Eaglesham C, Trench J, et al. A transferable psychological evaluation of virtual reality applied to safety training in chemical manufacturing. ACS Chem Health Saf. 2021;28(1):55–65.
  • Bird JM. The use of virtual reality head-mounted displays within applied sport psychology. J Sport Psychol Action. 2020;11(2):115–128.
  • Hilty DM, Randhawa K, Maheu MM, et al. A review of telepresence, virtual reality, and augmented reality applied to clinical care. J Technol Behav Sci. 2020;5(2):178–205.
  • Moro C, Štromberga Z, Raikos A, et al. The effectiveness of virtual and augmented reality in health sciences and medical anatomy. Anat Sci Educ. 2017;10(6):549–559.
  • Desselle MR, Brown RA, James AR, et al. Augmented and virtual reality in surgery. Comput Sci Eng. 2020;22(3):18–26.
  • Calvelo M, Á P, Garcia-Fandino R. An immersive journey to the molecular structure of SARS-CoV-2: virtual reality in COVID-19. Comput Struct Biotechnol J. 2020;18:2621–2628
  • Tse C-M, Li H, Leung K-S , et al., editors. Interactive drug design in virtual reality. 15th International Conference on Information Visualisation, London, UK; 2011: IEEE.
  • Zonta N, Brancale A. Virtual reality applications in antiviral drug design. Antiviral Res. 2009;82(2):A74.
  • Kleinberg ML, Wanke LA. New approaches and technologies in drug design and discovery. Am J Health Syst Pharm. 1995;52(12):1323–1336.
  • Cassidy KC, Šefčík J, Raghav Y, et al., ProteinVR: web-based molecular visualization in virtual reality. PLoS Comput Biol. 2020;16(3): e1007747
  • Kingsley LJ, Brunet V, Lelais G, et al. Development of a virtual reality platform for effective communication of structural data in drug discovery. J Mol Graphics Modell. 2019;89:234–241
  • O’Connor MB, Bennie SJ, Deeks HM, et al., Interactive molecular dynamics in virtual reality from quantum chemistry to drug binding: an open-source multi-person framework. J Chem Phys. 2019;150(22): 220901
  • Paper VR: VR storm studio; 2021 [2021 18 October]. Available from: https://vrstorm.hu/en/paper-vr/
  • Samsung gear VR: samsung; 2021 [2021 18 October]. Available from: https://www.samsung.com/global/galaxy/gear-vr/
  • Google cardboard: google; 2021 [18/January/2021]. Available from: https://arvr.google.com/cardboard/
  • Cruz-Neira C, Sandin DJ, DeFanti TA, et al. The CAVE: audio visual experience automatic virtual environment. Commun ACM. 1992;35(6):64–73.
  • Origin by vicon: vicon; [31/January/2022]. Available from: https://www.vicon.com/applications/location-based-virtual-reality
  • Liu X-H, Wang T, Lin J-P, et al. Using virtual reality for drug discovery: a promising new outlet for novel leads. Expert Opin Drug Discov. 2018;13(12):1103–1114.
  • Gaudiosi J. Dassault Systèmes Uses HTC vive to replace cave virtual reality tech. Fortune. 2016.
  • Arcane. Immersive projection-based virtual reality (VR) for everyone, mobile and tailor-made 2022 [31/January/2022]. Available from: https://arcanetech.io/produit/vr-cave/
  • Mestre DR. CAVE versus head-mounted displays: ongoing thoughts. Electron Imaging. 2017;2017(3):31–35.
  • Robertson A. Oculus rift S review: a swan song for first-generation VR: The Verge; 2019 2022 January 31. Available from: https://www.theverge.com/2019/4/30/18523941/oculus-rift-s-review-vr-headset-price-specs-features
  • Valve. Valve Index VR Kit Steam2022 [31/January/2022]. Available from: https://store.steampowered.com/sub/354231
  • Vive. Vive pro series vive2022 [31/January/2022]. Available from: https://www.vive.com/uk/product/#pro%20series
  • Angelov V, Petkov E, Shipkovenski G, et al., editors. Modern virtual reality headsets. 2020 international congress on human-computer interaction, Optimization and Robotic Applications (HORA). 2020: IEEE
  • Mehrfard A, Fotouhi J, Taylor G, et al. A comparative analysis of virtual reality head-mounted display systems. arXiv preprint arXiv. 2019;191202913.
  • HTC Vive Pro: Vive; 2021 [2021 13 September]. Available from: https://www.vive.com/uk/product/
  • Valve Index: Valve Software; 2021 [2021 13 September]. Available from: https://www.valvesoftware.com/en/index
  • Oculus Quest 2: Oculus VR; 2021 2021 September 13. Available from: https://www.oculus.com/quest-2/
  • Introducing meta: a social technology company: meta; 2021 [2021 December 11]. Available from: https://about.fb.com/news/2021/10/facebook-company-is-now-meta/
  • Stephenson N. Snow crash. United States: Bantam Books; 1992.
  • O’Connor M, Deeks HM, Dawn E, et al., Sampling molecular conformations and dynamics in a multiuser virtual reality framework. Sci Adv. 2018;4(6): eaat2731.
  • Hušák M, editor The use of stereoscopic visualization in chemistry and structural biology. Stereoscopic displays and virtual reality systems XIII. International Society for Optics and Photonics; 2006.
  • Zhu X, Li H, Huang L, et al. 3D printing promotes the development of drugs. Biomed Pharmacother. 2020;131:110644.
  • Freire R, Glowacki BR, Williams RR, et al. Omg-vr: open-source mudra gloves for manipulating molecular simulations in vr. arXiv preprint arXiv. 2019;190103532.
  • Norrby M, Grebner C, Eriksson J, et al., Molecular rift: virtual reality for drug designers. J Chem Inf Model. 2015;55(11): 2475–2484.
  • Microsoft kinect: microsoft; 2021 [ 29/10/21]. Available from: https://developer.microsoft.com/en-us/windows/kinect/
  • Stone RJ, editor Haptic feedback: a brief history from telepresence to virtual reality. International Workshop on Haptic Human-Computer Interaction, Glasgow, UK. Springer; 2000.
  • Burdea GC Force and touch feedback for virtual reality. 1996
  • Chinello F, Malvezzi M, Prattichizzo D, et al. A modular wearable finger interface for cutaneous and kinesthetic interaction: control and evaluation. IEEE Trans Ind Electron. 2019;67(1):706–716.
  • Whitmire E, Benko H, Holz C, et al., editors. Haptic revolver: touch, shear, texture, and shape rendering on a reconfigurable virtual reality controller. Proceedings of the 2018 CHI Conference on Human Factors in Computing Systems, Montreal, QC, Canada; 2018.
  • Al Maimani A, Roudaut A, editors. Frozen suit: designing a changeable stiffness suit and its application to haptic games. Proceedings of the 2017 CHI Conference on Human Factors in Computing Systems, Denver, Colorado, USA; 2017.
  • Al-Sada M, Jiang K, Ranade S, et al. HapticSnakes: multi-haptic feedback wearable robots for immersive virtual reality. Virtual Reality. 2020;24(2):191–209.
  • Spagnoletti G, Meli L, Baldi TL, et al., editors. Rendering of pressure and textures using wearable haptics in immersive vr environments. 2018 IEEE Conference on Virtual Reality and 3D User Interfaces (VR), Reutlingen, Germany; 2018: IEEE.
  • Pacchierotti C, Sinclair S, Solazzi M, et al. Wearable haptic systems for the fingertip and the hand: taxonomy, review, and perspectives. IEEE Trans Haptics. 2017;10(4):580–600.
  • HaptX Gloves DK2: haptX Inc.; 2021 [ 29/10/21]. Available from: https://haptx.com/virtual-reality/
  • Kreimeier J, Hammer S, Friedmann D, et al., editors. Evaluation of different types of haptic feedback influencing the task-based presence and performance in virtual reality. Proceedings of the 12th ACM International Conference on PErvasive Technologies Related to Assistive Environments, Rhodes, Greece; 2019.
  • Alaker M, Wynn GR, Arulampalam T. Virtual reality training in laparoscopic surgery: a systematic review & meta-analysis. Int J Surg. 2016;29:85–94.
  • Vaughan N, Dubey VN, Wainwright TW, et al. A review of virtual reality based training simulators for orthopaedic surgery. Med Eng Phys. 2016;38(2):59–71.
  • Pusch A, Lécuyer A, editors. Pseudo-haptics: from the theoretical foundations to practical system design guidelines. Proceedings of the 13th international conference on multimodal interfaces, New York, USA; 2011.
  • Lécuyer A, Coquillart S, Kheddar A, et al., editors. Pseudo-haptic feedback: can isometric input devices simulate force feedback? Proceedings IEEE Virtual Reality 2000 (Cat. No. 00CB37048), New Jersey, USA; 2000: IEEE.
  • Lécuyer A. Simulating haptic feedback using vision: a survey of research and applications of pseudo-haptic feedback. Presence: Teleoperators and Virtual Environments. 2009;18(1):39–53.
  • Roebuck Williams R, Varcoe X, Glowacki BR, et al., editors. Subtle sensing: detecting differences in the flexibility of virtually simulated molecular objects. Extended Abstracts of the 2020 CHI Conference on Human Factors in Computing Systems, Hawaii, USA; 2020
  • Humphrey W, Dalke A, Schulten K. VMD: visual molecular dynamics. J Mol Graph. 1996;14(1):33–38.
  • Trott O, Olson AJ. AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. J Comput Chem. 2010;31(2):455–461.
  • Karplus M, Kuriyan J. Molecular dynamics and protein function. Proc Nat Acad Sci. 2005;102(19):6679–6685.
  • Hernández-Rodríguez M, C Rosales-Hernández M, E Mendieta-Wejebe J, et al. Current tools and methods in molecular dynamics (MD) simulations for drug design. Curr Med Chem. 2016;23(34):3909–3924.
  • Durrant JD, McCammon JA. Molecular dynamics simulations and drug discovery. BMC Biol. 2011;9(1):1–9.
  • Liu X, Shi D, Zhou S, et al. Molecular dynamics simulations and novel drug discovery. Expert Opin Drug Discov. 2018;13(1):23–37.
  • De Vivo M, Masetti M, Bottegoni G, et al. Role of molecular dynamics and related methods in drug discovery. J Med Chem. 2016;59(9):4035–4061.
  • DeLano WL. Pymol: an open-source molecular graphics tool. CCP4 Newsletter on Protein Crystallography. 2002;40(1):82–92.
  • Pettersen EF, Goddard TD, Huang CC, et al. UCSF Chimera—a visualization system for exploratory research and analysis. J Comput Chem. 2004;25(13):1605–1612.
  • Goddard TD, Huang CC, Meng EC, et al., UCSF ChimeraX: meeting modern challenges in visualization and analysis. Protein Sci. 2018;27(1): 14–25.
  • Pettersen EF, Goddard TD, Huang CC, et al. UCSF ChimeraX: structure visualization for researchers, educators, and developers. Protein Sci. 2021;30(1):70–82.
  • Radić Z, Kirchhoff PD, Quinn DM, et al. Electrostatic influence on the kinetics of ligand binding to acetylcholinesterase: distinctions between active center ligands and fasciculin. J Biol Chem. 1997;272(37):23265–23277.
  • Zhou H-X, Pang X. Electrostatic interactions in protein structure, folding, binding, and condensation. Chem Rev. 2018;118(4):1691–1741.
  • Náray‐szabó G. Electrostatics in computer‐aided drug design. Int J Quantum Chem. 1989;36(S16):87–99.
  • Rathi PC, Ludlow RF, Verdonk ML. Practical high-quality electrostatic potential surfaces for drug discovery using a graph-convolutional deep neural network. J Med Chem. 2019;63(16):8778–8790.
  • Doak DG, Denyer GS, Gerrard JA, et al., Peppy: a virtual reality environment for exploring the principles of polypeptide structure. Protein Sci. 2020;29(1): 157–168.
  • Kneller DW, Li H, Galanie S, et al., Structural, electronic, and electrostatic determinants for inhibitor binding to subsites s1 and s2 in sars-Cov-2 main protease. J Med Chem. 2021;64(23): 17366–17383.
  • Collaborating for coronavirus drug discovery California: oculus; cited 2022 Apr 13]. Available from 2022 Apr 13: https://business.oculus.com/case-studies/novartis/?locale=en_GB
  • Accelerating drug discovery to create a healthier future California: Oculus; cited 2022 Apr 13]. Available from 2022 Apr 13: https://business.oculus.com/case-studies/nimbus/?locale=en_GB
  • Roivant in largest ever deployment of Nanome VR drug discovery software London UK: VRWorldTech; cited 2022 Apr 13]. Available from 2022 Apr 13: https://vrworldtech.com/2021/12/17/roivant-in-largest-ever-deployment-of-nanome-vr-drug-discovery-software/
  • Castellanos S. Virtual reality puts drug researchers inside the molecules they study. Wall Street Journal. Sep 7. 2021. [cited 25 05 2022]. https://www.wsj.com/articles/virtual-reality-puts-drug-researchers-inside-the-molecules-they-study-11631023212
  • Grier F Nanome partners with Fujitsu, San Diego: San Diego Business Journal 2020 cited 2022 Apr 13]. Available from 2022 Apr 13: https://www.sdbj.com/news/2020/sep/15/nanome-partners-fujitsu/
  • Fried SD, Boxer SG. Electric fields and enzyme catalysis. Annu Rev Biochem. 2017;86:387–415.
  • Weiner PK, Langridge R, Blaney JM, et al. Electrostatic potential molecular surfaces. Proc Nat Acad Sci. 1982;79(12):3754–3758.
  • Bauer MR, Mackey MD. Electrostatic complementarity as a fast and effective tool to optimize binding and selectivity of protein–ligand complexes. J Med Chem. 2019;62(6):3036–3050.
  • Nakamura H, Komatsu K, Nakagawa S, et al. Visualization of electrostatic recognition by enzymes for their ligands and cofactors. J Mol Graph. 1985;3(1):2–11.
  • Keil M, Marhofer RJ, Rohwer A, et al. Molecular visualization in the rational drug design process. Front Biosci. 2009;14:2559–2583.
  • Jurrus E, Engel D, Star K, et al. Improvements to the APBS biomolecular solvation software suite. Protein Sci. 2018;27(1):112–128.
  • Unni S, Huang Y, Hanson RM, et al. Web servers and services for electrostatics calculations with APBS and PDB2PQR. J Comput Chem. 2011;32(7):1488–1491.
  • Dolinsky TJ, Nielsen JE, McCammon JA, et al. PDB2PQR: an automated pipeline for the setup of Poisson–Boltzmann electrostatics calculations. Nucleic Acids Res. 2004;32(suppl_2):W665–W667.
  • Laureanti J, Brandi J, Offor E, et al., Visualizing biomolecular electrostatics in virtual reality with unitymol‐APBS. Protein Sci. 2020;29(1): 237–246.
  • Loging WT. The art and science of the drug discovery pipeline: history of drug discovery. Bioinformatics and Computational Biology in Drug Discovery and Development. 2016;1.
  • Chang Y-S, Chou C-H, Chuang M-J, et al. Effects of virtual reality on creative design performance and creative experiential learning. Interact Learn Environ. 2020; 28:1–16.
  • Yang X, Lin L, Cheng P-Y, et al. Examining creativity through a virtual reality support system. Edu Technol Res Develop. 2018;66(5):1231–1254.
  • Berg JM, Tymoczko JL, Stryer L. Biochemistry. New York: WH Freeman; 2002.
  • Pagadala NS, Syed K, Tuszynski J. Software for molecular docking: a review. Biophys Rev. 2017;9(2):91–102.
  • Kutak D, Selzer MN, Byska J, et al. Vivern A virtual environment for multiscale visualization and modeling of DNA nanostructures. 2021. https://ieeexplore.ieee.org/document/9523759
  • Juárez-Jiménez J, Tew P, Llabres S, et al. A virtual reality ensemble molecular dynamics workflow to study complex conformational changes in proteins. 2020.
  • Stone JE, Gullingsrud J, Schulten K, editors. A system for interactive molecular dynamics simulation. Proceedings of the 2001 symposium on Interactive 3D graphics, New York, USA; 2001
  • Rapaport D. Interactive molecular dynamics. Phys A Stat Mech Appli. 1997;240(1–2):246–254.
  • Vormoor O. Quick and easy interactive molecular dynamics using Java3D. Computing Sci Eng. 2001;3(5):98–104.
  • Knoll P, Mirzaei S. Development of an interactive molecular dynamics simulation software package. Rev Sci Instrum. 2003;74(4):2483–2487.
  • Schroeder DV. Interactive molecular dynamics. Am J Phys. 2015;83(3):210–218.
  • Croll TI, Andersen GR. Re-evaluation of low-resolution crystal structures via interactive molecular-dynamics flexible fitting (iMDFF): a case study in complement C4. Acta Crystallograph Sect D: Struct Biol. 2016;72(9):1006–1016.
  • Izrailev S, Stepaniants S, Isralewitz B, et al. Steered molecular dynamics. Computational molecular dynamics: challenges, methods, ideas. Springer; 1999. p. 39–65.
  • Grayson P, Tajkhorshid E, Schulten K. Mechanisms of selectivity in channels and enzymes studied with interactive molecular dynamics. Biophys J. 2003;85(1):36–48.
  • Ai Z, Fröhlich T, editors Molecular dynamics simulation in virtual environments. Computer graphics forum. Wiley Online Library; 1998.
  • Hamdi M, Ferreira A, Sharma G, et al. Prototyping bio-nanorobots using molecular dynamics simulation and virtual reality. Microelectronics J. 2008;39(2):190–201.
  • Dreher M, Piuzzi M, Turki A, et al. Interactive molecular dynamics: scaling up to large systems. Procedia Comput Sci. 2013;18:20–29.
  • Seritan S, Wang Y, Ford JE, et al., InteraChem: virtual reality visualizer for reactive interactive molecular dynamics. J Chem Educ. 2021;98(11): 3486–3492.
  • Ferrell JB, Campbell JP, McCarthy DR, et al. Chemical exploration with virtual reality in organic teaching laboratories. J Chem Educ. 2019;96(9):1961–1966.
  • Luehr N, Jin AG, Martínez TJ. Ab initio interactive molecular dynamics on graphical processing units (GPUs). J Chem Theory Comput. 2015;11(10):4536–4544.
  • Phillips JC, Braun R, Wang W, et al. Scalable molecular dynamics with NAMD. J Comput Chem. 2005;26(16):1781–1802.
  • Jamieson-Binnie AD, O’Connor MB, Barnoud J, et al. Narupa iMD: a VR-enabled multiplayer framework for streaming interactive molecular simulations. ACM SIGGRAPH 2020 Immersive Pavilion. 2020;1–2.
  • Eastman P, Swails J, Chodera JD, et al. OpenMM 7: rapid development of high performance algorithms for molecular dynamics. PLoS Comput Biol. 2017;13(7):e1005659.
  • Bennie SJ, Ranaghan KE, Deeks H, et al., Teaching enzyme catalysis using interactive molecular dynamics in virtual reality. J Chem Educ. 2019;96(11): 2488–2496.
  • Schneider G, Böhm H-J. Virtual screening and fast automated docking methods. Drug Discov Today. 2002;7:64–70.
  • Goodsell DS, Morris GM, Olson AJ. Automated docking of flexible ligands: applications of autodock. J Mol Recog. 1996;9(1):1–5.
  • Blaney JM, Dixon JS. A good ligand is hard to find: automated docking methods. Perspect Drug Discovery Des. 1993;1(2):301–319.
  • Goodsell DS, Olson AJ. Automated docking of substrates to proteins by simulated annealing. Proteins Struct Funct Bioinf. 1990;8(3):195–202.
  • Deeks HM, Walters RK, Hare SR, et al., Interactive molecular dynamics in virtual reality for accurate flexible protein-ligand docking. Plos one. 2020;15(3): e0228461.
  • Deeks HM, Walters RK, Barnoud J, et al., Interactive molecular dynamics in virtual reality is an effective tool for flexible substrate and inhibitor docking to the SARS-CoV-2 main protease. J Chem Inf Model. 2020;60(12): 5803–5814.
  • Zhang L, Lin D, Sun X, et al. Crystal structure of SARS-CoV-2 main protease provides a basis for design of improved α-ketoamide inhibitors. Science. 2020;368(6489):409–412.
  • Chan HH, Moesser MA, Walters RK, et al. Discovery of SARS-Cov-2 mpro peptide inhibitors from modelling substrate and ligand binding. Chemical science. 2021;12.
  • Discovery C4X. The 4Sight project: using VR in the drug discovery space: immerse UK; [31/January/2022]. Available from: https://www.immerseuk.org/case-study/c4x-discovery/
  • Dutton GDail. DEMO: Nanome Triggers Deep Drug Development Insights Via Virtual Molecule Design. BioSpace. 2021. [cited 2022 May 25]. https://www.biospace.com/article/demo-nanome-inc-triggers-deep-drug-development-insights-via-virtual-molecule-design-/
  • Mitchell TJ, Jones AJ, O’Connor MB, et al., editors. Towards molecular musical instruments: interactive sonifications of 17-alanine, graphene and carbon nanotubes. Proceedings of the 15th International Conference on Audio Mostly, New York, USA; 2020.
  • Arbon RE, Jones AJ, Bratholm LA, et al. Sonifying stochastic walks on biomolecular energy landscapes. arXiv preprint arXiv. 2018;180305805.
  • Shannon RJ, Deeks HM, Burfoot E, et al. Exploring human-guided strategies for reaction network exploration: interactive molecular dynamics in virtual reality as a tool for citizen scientists. J Chem Phys. 2021;155(15):154106.