Ram Samudrala

Ram Samudrala is a professor of computational biology and bioinformatics at the University at Buffalo, and formerly at the University of Washington in Seattle, United States.[3] He researches protein and proteome folding, structure, function, interaction, design, and evolution spanning atomic to organismal levels of description.[4] He has published more than 140 manuscripts[5] in a variety of journals including Science,[6] Nature,[7] PLoS Biology,[8] Drug Discovery Today,[9] the Proceedings of the National Academy of Sciences,[10] and the Journal of the American Medical Association.[11]

Ram Samudrala
Born (1972-03-23) March 23, 1972
Alma materOhio Wesleyan University, Center for Advanced Research in Biotechnology, Stanford University
Known forAll atom knowledge based simulations, structural systems biology, computational drug discovery, free music philosophy
Awards
Scientific career
FieldsComputational biology
InstitutionsUniversity at Buffalo, University of Washington
Doctoral advisorJohn Moult
Other academic advisorsMichael Levitt
InfluencesDouglas Hofstadter, Richard Stallman
Websiteram.org
compbio.org

Samudrala is also a musician who has published and recorded work under the pseudonym TWISTED HELICES.[12] In 1994, he published the Free music Philosophy,[13] which accurately predicted how the ease of copying and transmitting digital information by the Internet would lead to unprecedented violations of copyright laws and new models of distribution for music and other digital media.[14][15][16] His work in this area was reported as early as 1997 by diverse media outlets including Billboard,[17] Forbes,[18] Levi's Original Music Magazine,[19] The Free Radical,[20] Wired[21][22] and The New York Times.[23]

Education and career

Prior to joining the faculty at the University of Washington, Samudrala was a post-doctoral fellow with Michael Levitt at Stanford University from 1997–2000, with a fellowship from the Program in Mathematics and Molecular Biology (funded by the NSF and the Burroughs Wellcome Fund). He received his undergraduate degrees in Computing Science and Genetics from Ohio Wesleyan University (1990–1993) as a Wesleyan Scholar, and completed his Ph.D. in Computational Structural Biology with John Moult at the Center for Advanced Research in Biotechnology in Rockville, MD (1993–1997) as a Life Technologies Fellow. In 2001, Samudrala became the first faculty member to be recruited, as an Assistant Professor, under the Advanced Technology Initiative in Infectious Diseases created by the Washington State Legislature "as a bridge between cutting-edge research and education, and new economic activity."[24] He was promoted to Associate Professor with tenure in 2006. In 2014, he became Professor and Chief of the Division of Bioinformatics at the State University of New York, Buffalo.[5]

Awards and honours

Samudrala received a Searle Scholar Award which funds exceptional young scientists in 2002,[1] was named one of the world's top young innovators (TR100) by MIT Technology Review in 2003,[2][25][26] and was selected to present the University of Washington New Investigator Science in Medicine Lecture in 2004.[27] In 2005, he received a NSF CAREER Award[28] which recognizes "outstanding scientists and engineers who show exceptional potential for leadership at the frontiers of knowledge". In 2008, he received the Alberta Heritage Foundation for Medical Research Visiting Scientist Award and was awarded honorary diplomas from the cities of Casma and Yautan, Peru, for his work on vaccine discovery. He was a NIH Director's Pioneer Award[29] finalist in 2006 (25/465 applicants were selected as finalists) for a novel idea to determine the structures of all proteins in a solution that he then presented at the seventh community wide assessment of protein structure prediction methods (CASP7).[30] In 2010, he again became a finalist and went on to receive the Pioneer Award for his Computational Analysis of Novel Drug Opportunities (CANDO) drug discovery platform[31] to screen every known drug against every known target structure in a shotgun manner to discover new repurposeable therapeutics,[9] particularly for underserved diseases. That same year, he received the Best Undergraduate Research Mentor Award from the University of Washington. In 2019, Samudrala was named a University at Buffalo Exceptional Scholar [32][5] and also awarded a NIH NCATS ASPIRE Design Challenge Award.[33][5]

Research

Samudrala's research has focused on understanding how the genome of an organism specifies its behaviour and characteristics, and applying that information to improve health and quality of life. His vision is to produce a computing model of life focused on atomic level detail, organisation, and arrangements of all the components involved, which he calls the "structeome". The structeome, which is the actual structural organization of components at the atomic level, by its very nature includes single molecules such as DNA, RNA, proteins, and metabolites, as well larger groupings such genomes, proteome, interactomes, connectomes, and so on. Since the vision is of a large collection of atoms with subgroupings of atoms that work together in a complex dynamic manner, a protein would be a collection of atoms, many of which are covalently bonded, that interact together to perform a specific biological function. Samudrala's work has thus focussed on proteins, which is the fundamental unit of biological function within the structeome. Atoms in a structeome interact with the environment which may include other structeomes (or components thereof) thereby causing a strange loop or a tangled hierarchy of interactions. Thus a structeome would include not only all atoms and their interactions within that structeome, but also all interactions to other structeomes. Samudrala has extended this theoretical framework to explain how evolution works by recursion of existing information and has used it to solve research problems with practical applications in medicine, such as therapeutic discovery based on docking with dynamics,[34] multitargeting, and drug repurposing in a shotgun manner,[9][11][31][35][36] as well as in nanobiotechnology, such as engineering tooth tissue by designing novel peptides that bind to various inorganic substrates.[37][38]

Specifically, on a more grounded level, he has consistently taken part in, spoken at, and published in the proceedings of blind protein structure prediction experiments, known as CASP since its inception. His work with John Moult at CASP1[39] in 1994 and CASP2[40] in 1996 and with Michael Levitt at CASP3[41] in 1998 are among the first improvements of blinded protein structure prediction in both comparative and template free modelling categories. With John Moult, as part of his PhD thesis, he was the first to develop and apply an all heavy atom knowledge-based conditional probability discriminatory function [42] as well as graph-theoretic methods [43] to accurately predict interactomic interactions for comparative modelling of protein structures. With Michael Levitt, as part of his postdoctoral fellowship, he developed a combined hierarchical approach for de novo structure prediction [44] as well as the Decoys 'R' Us database to evaluate discrimination functions.[45]

After he joined the faculty of the University of Washington, Samudrala's Computational Biology Research Group developed a series of algorithms and web server modules to predict protein structure,[46] function,[47] and interactions[48] known as Protinfo.[49][50]

Samudrala's group then applied these methods to entire organismal proteomes, creating a framework known as the Bioverse[51][52] for exploring the relationships among the atomic, molecular, genomic, proteomic, systems, and organismal worlds. The Bioverse framework performs sophisticated analyses and predictions based on genomic sequence data to annotate and understand the interaction of protein sequence, structure, and function, both at the single molecule as well as at the systems levels. A set of first pass predictions is available for more than 50 organismal proteomes and the framework was used to annotate the finished rice genome sequence published in 2005.[8] He is currently working on integrating a vast amount of protein interaction data (to other proteins, DNA, RNA, and smaller ligands) and modelling them at the atomic level. The end goal of the Bioverse project is to understand and simulate life at an atomic level. A subset of this atomic level interactome, consisting of a large set human ingestible small molecules and a set of structures representing the protein universe, has already been constructed as part of the drug discovery platform described below.

Finally, Samudrala's group has pioneered the successful applications of these basic science methods to drug discovery, including the Computational Analysis of Novel Drug Opportunities (CANDO) platform funded by a 2010 NIH Director's Pioneer Award that ranks therapeutics for all indications by analysis and comparison of structural compound-proteome interaction signatures.[9][31][36][53] A combination of novel docking methods and/or its use in the CANDO platform has led to prospectively validated predictions of putative drugs against dengue,[54][55] dental caries, herpes, lupus, and malaria[35] along with indication-specific collaborators.[56]

Other successful areas of application include medicine, predicting HIV drug resistance/susceptibility;[57] nanobiotechnology, where small multifunctional peptides that bind to inorganic substrates are designed computationally;[37][38][58] and interactomics of several organisms, including the Nutritious Rice for the World (NRW) project[59] where protein structure prediction methods are applied to all tractable proteins encoded by the rice genome on the IBM World Community Grid as well as the 1KP project to predict protein structures. functions, and interactions of 1000 plant proteomes.[60] The NRW project harnessed the power of individual PCs via the Grid to perform its computations to help design better rice strains with higher yield and range of bioavailable nutrients, and was covered by more than 200 media outlets worldwide[61] including The New York Times,[62] BusinessWeek,[63] NSF,[64] The Times of India,[65] and Fortune.[66]

References
  1. Searle Scholar Award profile for Ram Samudrala
  2. MIT Technology Review Profile naming Ram Samudrala one of the world's top young innovators
  3. Ram Samudrala's personal web site
  4. Samudrala Computational Biology Group
  5. Ram Samudrala's curriculum vitae
  6. Wang K, Mittler J, Samudrala R. Comment on "Evidence for positive epistasis in HIV-1". Science 312: 848b, 2006.
  7. Wang J, Zhang J, Zheng H, Li J, Liu D, Li H, Samudrala R, Yu J, Wong GK. Mouse transcriptome: Neutral evolution of "non-coding" complementary DNAs. Nature 431, 2004.
  8. Yu J, Wang J, Lin W, Li S, Li H, Zhou J, ..., McDermott J, Samudrala R, Wang J, Wong GK. The genomes of Oryza sativa: A history of duplications. PLoS Biology 3: e38, 2005.
  9. Minie M, Chopra G, Sethi G, Horst J, White G, Roy A, Hatti K, Samudrala R. CANDO and the infinite drug discovery frontier. "Drug Discovery Today" 19: 1353-1363, 2014.
  10. Jenkins C, Samudrala R, Anderson I, Hedlund BP, Petroni G, Michailova N, Pinel N, Overbeek R, Rosati G, Staley JT. Genes for the cytoskeletal protein tubulin in the bacteria genus Prosthecobacter. Proceedings of the National Academy of Sciences 99: 17049-17054, 2002.
  11. Jenwitheesuk E, Samudrala R. Identification of potential multitarget antimalarial drugs. Journal of the American Medical Association 294: 1490-1491, 2005.
  12. TWISTED HELICES
  13. Free Music Philosophy
  14. Samudrala R. The future of music, 1997
  15. Story of a Revolution: Napster & the Music Industry. MusicDish, 2000
  16. Schulman BM. The song heard 'round the world: The copyright implications of MP3s and the future of digital music. Harvard Journal of Law and Technology 12: 3, 1999. Archived 2012-04-09 at the Wayback Machine
  17. Reece D. Industry grapples with MP3 dilemma. Billboard, July 18 1998.
  18. Penenberg A. Habias copyrightus. Forbes, July 11 1997.
  19. Durbach D. Short fall to freedom: The free music insurgency. Levi's Original Music Magazine, November 19, 2008. Archived June 1, 2010, at the Wayback Machine
  20. Ballin M. Unfair Use. The Free Radical 47, 2001.
  21. Oakes C. Recording industry goes to war against web sites. Wired, June 10 1997.
  22. Stutz M. They (used to) write the songs. Wired, June 12 1998.
  23. Napoli L. Fans of MP3 forced the issue. The New York Times, December 16 1998.
  24. Roseth B. Funding forward vision. University Week, March 1 2001. Archived 2011-06-04 at the Wayback Machine
  25. Kurian V. 10 Indian innovators in MIT list. The Hindu Business Line, October 4 2003.
  26. 10 of Indian Origin in MIT's Technology Review. Hindustan Times, March 1 2007. Archived 2010-08-23 at the Wayback Machine
  27. Dietz C. How genomes make proteomes. University Week 22: 17, 2005.
  28. CAREER Award
  29. NIH Director's Pioneer Award
  30. Shotgun structural proteomics. NIH Director's Pioneer Award finalist interview for Ram Samudrala, Bethesda, MD. August 9, 2006.
  31. Computational analysis of novel drug opportunities (CANDO)
  32. UB honors exceptional scholars, innovative teachers, July 12 2019.
  33. NIH HEAL Initiative issues awards to UB researchers to develop non-addictive painkillers, September 30 2019.
  34. Jenwitheesuk E, Samudrala R. Improved prediction of HIV-1 protease-inhibitor binding energies by molecular dynamics simulations. BMC Structural Biology 3: 2, 2003.
  35. Jenwitheesuk E, Horst JA, Rivas K, Van Voorhis WC, Samudrala R. Novel paradigms for drug discovery: Computational multitarget screening. Trends in Pharmacological Sciences 29: 62-71, 2008.
  36. Sethi G, Chopra G, Samudrala R. Multiscale modelling of relationships between protein classes and drug behavior across all diseases using the CANDO platform. Mini Reviews in Medicinal Chemistry, 2015. in press.
  37. Cementomimetics-constructing a cementum-like biomineralized microlayer via amelogenin-derived peptides. Gungormus M, Oren EE, Horst JA, Fong H, Hnilova M, Somerman MJ, Snead ML, Samudrala R, Tamerler C, Sarikaya M. International Journal of Oral Sciences 2: 69-77, 2012.
  38. Oren EE, Tamerler C, Sahin D, Hnilova M, Seker UOS, Sarikaya M, Samudrala R. A novel knowledge-based approach for designing inorganic binding peptides. Bioinformatics 23: 2816-2822, 2007.
  39. Samudrala R, Pedersen JT, Zhou H, Luo R, Fidelis K, Moult J. Confronting the problem of interconnected structural changes in the comparative modelling of proteins. Proteins: Structure, Function, and Genetics 23: 327-336, 1995.
  40. Samudrala R, Moult J. Handling context-sensitivity in protein structures using graph theory: bona fide prediction. Proteins: Structure, Function, and Genetics 29S: 43-49, 1997.
  41. Samudrala R, Xia Y, Huang ES, Levitt M. Ab initio prediction of protein structure using a combined hierarchical approach. Proteins: Structure, Function, and Genetics S3: 194-198, 1999.
  42. Samudrala R, Moult J. An all-atom distance-dependent conditional probability discriminatory function for protein structure prediction. Journal of Molecular Biology 275: 893-914, 1998.
  43. Samudrala R, Moult J. A graph-theoretic algorithm for comparative modelling of protein structure. Journal of Molecular Biology 279: 287-302, 1998.
  44. Xia Y, Huang ES, Levitt M, Samudrala R. Ab initio construction of protein tertiary structures using a hierarchical approach. Journal of Molecular Biology 300: 171-185, 2000.
  45. Samudrala R, Levitt M. Decoys 'R' Us: A database of incorrect protein conformations to improve protein structure prediction. Protein Science 9: 1399-1401, 2000.
  46. Liu T, Horst J, Samudrala R. A novel method for predicting and using distance constraints of high accuracy for refining protein structure prediction. Proteins: Structure, Function, and Bioinformatics 77: 220-234, 2009.
  47. Wang K, Horst J, Cheng G, Nickle D, Samudrala R. Protein meta-functional signatures from combining sequence, structure, evolution and amino acid property information. PLoS Computational Biology 4: e1000181, 2008.
  48. Kittichotirat W, Guerquin M, Bumgarner R, Samudrala R. Protinfo PPC: A web server for atomic level prediction of protein complexes. Nucleic Acids Research 37: W519-W525, 2009.
  49. Hung L-H, Samudrala R. PROTINFO: Secondary and tertiary protein structure prediction. Nucleic Acids Research 31: 3296-3299, 2003.
  50. Hung L-H, Ngan S-C, Liu T, Samudrala R. PROTINFO: New algorithms for enhanced protein structure prediction. Nucleic Acids Research 33: W77-W80, 2005.
  51. McDermott J, Samudrala R. BIOVERSE: Functional, structural, and contextual annotation of proteins and proteomes. Nucleic Acids Research 31: 3736-3737, 2003.
  52. McDermott J, Guerquin M, Frazier Z, Chang AN, Samudrala R. BIOVERSE: Enhancements to the framework for structural, functional, and contextual annotations of proteins and proteomes. Nucleic Acids Research 33: W324-W325, 2005.
  53. Horst JA, Laurenzi A, Bernard B, Samudrala R. Computational multitarget drug discovery. "Polypharmacology "263-301, 2012.
  54. Costin JM, Jenwitheesuk E, Lok S-M, Hunsperger E, Conrads KA, Fontaine KA, Rees CR, Rossmann MG, Isern S, Samudrala R, Michael SF. Structural optimization and de novo design of dengue virus entry inhibitory peptides. PLoS Neglected Tropical Diseases 4: e721, 2010.
  55. Nicholson CO, Costin JM, Rowe DK, Lin L, Jenwitheesuk E, Samudrala R, Isern S, Michael SF. Viral entry inhibitors block dengue antibody-dependent enhancement in vitro. Antiviral Research 89: 71-74, 2011.
  56. Computational analysis of novel drug opportunities (CANDO) indications and collaborations
  57. Jenwitheesuk E, Wang K, Mittler J, Samudrala R. PIRSpred: A webserver for reliable HIV-1 protein-inhibitor resistance/susceptibility prediction. Trends in Microbiology 13: 150-151, 2005.
  58. Evans JS, Samudrala R, Walsh TR, Oren EE, Tamerler C. Molecular design of inorganic-binding polypeptides. MRS Bulletin 33: 514-518, 2008.
  59. Nutritious Rice for the World web site
  60. Matasci N, Hung L-H, ..., Samudrala R, Tian Z, Wu X, Sun X, Zhang Y, Wang J, Leebens-Mack J, Wong GSK. Data access for the 1,000 Plants (1KP) project. Gigascience 3: 17, 2014.
  61. Nutritious Rice for the World press coverage
  62. Lohr S. Join the Hunt for Super-Rice. The New York Times, May 14 2008.
  63. Hamm S. IBM's Answer to the Food Crisis. Business Week, May 14 2008.
  64. Ram Samudrala and Michal Guerguin discuss the World Community Grid to study rice protein structures, NSF, Oct 16 2008.
  65. Rajghatta C. Help the poor, lend some computing time. The Times of India, May 19 2008.
  66. Gunther M. IBM: From supercomputers to superrice. Fortune, May 16 2008.
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