Jacobs School of Medicine and Biomedical Sciences

Ram Samudrala

Ram Samudrala PhD

Department of Biomedical Informatics

Professor and Chief, Division of Bioinformatics

Specialty/Research Focus

Bioinformatics

Overview Research Publications Activities Latest News

Professional Summary:

My group performs research to understand, through multiscale modelling, how organismal metagenomes specify their behavior and characteristics in conjunction with their environments. We accomplish this by developing novel computational biology and bioinformatics algorithms for predicting protein and proteome structure, function, interaction, design and evolution. We apply these basic science techniques to important practical problems in medicine, genetic and genomic engineering and nanobiotechnology.

I received the 2010 National Institutes of Health (NIH) Director‘s Pioneer Award to develop the Computational Analysis of Novel Drug Opportunities (CANDO) platform (http://protinfo.org/cando/) to repurpose drugs approved for other indications in a shotgun manner. Our integrated informatics platform determines interactions between and among all drugs and all protein structures to create compound-proteome interaction signatures. The compound-proteome interaction signatures are weighted using pharmacological, physiological and chemoinformatics data and compared and analyzed to predict the likelihood of the corresponding compounds being efficacious for all indications simultaneously, in effect inferring homology of drug behavior at a proteomic level.

Using this approach, we have made predictions for all the indications that our library of drugs maps to, with benchmarking accuracies that are two orders of magnitude better than what is observed when using random controls. We have performed prospective in vitro validations of our predictions, demonstrating comparable or better inhibition than existing drugs approved for clinical use in indications such as dengue, dental caries, diabetes, hepatitis B, herpes, lupus, malaria and tuberculosis. Our approach may be generalized to compounds beyond those approved by the FDA, and it can as well consider mutations in protein structures to enable precision medicine. We have also applied our computational techniques to design peptides for vaccines, antibacterial activity and inorganic substrate adhesion and model the structures, functions and interactions of all tractable proteins encoded by several rice genomes.

A consistent theme in our research is the combination of in virtuale simulation and homology inference, followed by in vitro and in vivo verification and application, directed toward holistic multiscale modelling of complex biological systems.

Education and Training:

Postdoctoral Fellow, Computational Biology, Stanford University (2000)
PhD, Computational Biology, Center for Advanced Research in Biotechnology (1997)
BA, Computer Science and Genetics, Ohio Wesleyan University (1993)

Employment:

Professor, Biomedical Informatics, University at Buffalo (2014-present)
Associate Professor, Microbiology, University of Washington (2006–2014)
Assistant Professor, Microbiology, University of Washington (2001–2006)
Post Doctoral Fellow, Stanford University, Medicine (1997–2001)
Fellow, University of Maryland, Center for Advanced Research in Biotechnology (1993–1997)

Awards and Honors:

NIH Director's Pioneer Award (2010)
Best Undergraduate Research Mentor Award at the University of Washington (2010)
NSF CAREER Award (2005)
World's Top Young Innovator Award (TR100) (2003)
Searle Scholar (2002)

Grants and Sponsored Research:

August 2015–August 2019
Buffalo Clinical and Translational Research Center Clinical and Translational Science Award(CTSA)
National Center for Advancing Translational Sciences (NCATS)/National Institutes of Health
Role: Co-Investigator
$20,000,000
September 2010–April 2017
Novel Paradigms for Drug Discovery: Computational Multitarget Screening
National Institute of Health
Role: Principal Investigator

Evaluative Studies and Case Reports:

Cheng G, Qian B, Samudrala R, Baker D. Improvement in protein functional site prediction by distinguishing structural and functional constraints on protein family evolution using computational design. Nucleic Acids Res. 2005; 33(18).
McDermott J, Bumgarner R, Samudrala R. Functional annotation from predicted protein interaction networks. Bioinformatics. 2005; 21(15).
Wang K, Samudrala R. FSSA: a novel method for identifying functional signatures from structural alignments. Bioinformatics. 2005; 21(13).
Jenwitheesuk E, Samudrala R. Improved prediction of HIV-1 protease-inhibitor binding energies by molecular dynamics simulations. BMC Struct Biol. 2003; 3.
Samudrala R, Levitt M. A comprehensive analysis of 40 blind protein structure predictions. BMC Struct Biol. 2002; 2.

Journal Articles:

Sethi G, Chopra G, Samudrala R. Multiscale modelling of relationships between protein classes and drug behavior across all diseases using the CANDO platform. Mini Rev Med Chem. 2015; 15(8).
Minie M, Chopra G, Sethi G, Horst J, White G, Roy A, Hatti K, Samudrala R. CANDO and the infinite drug discovery frontier. Drug Discov Today. 2014; 19(9).
Goldman AD, Baross JA, Samudrala R. The enzymatic and metabolic capabilities of early life. PLoS One. 2012; 7(9).
Gungormus M, Oren EE, Horst JA, Fong H, Hnilova M, Somerman MJ, Snead ML, Samudrala R, Tamerler C, Sarikaya M. Cementomimetics-constructing a cementum-like biomineralized microlayer via amelogenin-derived peptides. Int J Oral Sci. 2012; 4(2).
Horst JA, Samudrala R. A protein sequence meta-functional signature for calcium binding residue prediction. Pattern Recognit Lett. 2010; 31(14).
Costin JM, Jenwitheesuk E, Lok SM, 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 Negl Trop Dis. 2010; 4(6).
Liu T, Horst JA, Samudrala R. A novel method for predicting and using distance constraints of high accuracy for refining protein structure prediction. Proteins. 2009; 77(1).
Kittichotirat W, Guerquin M, Bumgarner RE, Samudrala R. Protinfo PPC: a web server for atomic level prediction of protein complexes. Nucleic Acids Res. 2009; 37(Web S).
Bernard B, Samudrala R. A generalized knowledge-based discriminatory function for biomolecular interactions. Proteins. 2009; 76(1).
Wang K, Horst JA, Cheng G, Nickle DC, Samudrala R. Protein meta-functional signatures from combining sequence, structure, evolution, and amino acid property information. PLoS Comput Biol. 2008; 4(9).
Jenwitheesuk E, Horst JA, Rivas KL, Van Voorhis WC, Samudrala R. Novel paradigms for drug discovery: computational multitarget screening. Trends Pharmacol Sci. 2008; 29(2).
Oren EE, Tamerler C, Sahin D, Hnilova M, Seker UO, Sarikaya M, Samudrala R. A novel knowledge-based approach to design inorganic-binding peptides. Bioinformatics. 2007; 23(21).
Hung LH, Samudrala R. An automated assignment-free Bayesian approach for accurately identifying proton contacts from NOESY data. J Biomol NMR. 2006; 36(3).
Hung LH, Ngan SC, Liu T, Samudrala R. PROTINFO: new algorithms for enhanced protein structure predictions. Nucleic Acids Res. 2005; 33(Web S).
McDermott J, Guerquin M, Frazier Z, Chang AN, Samudrala R. BIOVERSE: enhancements to the framework for structural, functional and contextual modeling of proteins and proteomes. Nucleic Acids Res. 2005; 33(Web S).
Jenwitheesuk E, Wang K, Mittler JE, Samudrala R. PIRSpred: a web server for reliable HIV-1 protein-inhibitor resistance/susceptibility prediction. Trends Microbiol. 2005; 13(4).
Wang K, Fain B, Levitt M, Samudrala R. Improved protein structure selection using decoy-dependent discriminatory functions. BMC Struct Biol. 2004; 4.
McDermott J, Samudrala R. Enhanced functional information from predicted protein networks. Trends Biotechnol. 2004; 22(2).
Huang ES, Samudrala R, Ponder JW. Ab initio fold prediction of small helical proteins using distance geometry and knowledge-based scoring functions. J Mol Biol. 1999; 290(1).
Samudrala R, Xia Y, Huang E, Levitt M. Ab initio protein structure prediction using a combined hierarchical approach. Proteins. 1999; Suppl.
Samudrala R, Moult J. An all-atom distance-dependent conditional probability discriminatory function for protein structure prediction. J Mol Biol. 1998; 275(5).
Samudrala R, Moult J. Handling context-sensitivity in protein structures using graph theory: bona fide prediction. Proteins. 1997; Suppl.
Samudrala R, Pedersen JT, Zhou HB, Luo R, Fidelis K, Moult J. Confronting the problem of interconnected structural changes in the comparative modeling of proteins. Proteins. 1995; 23(3).
Craig JK, Risler JK, Loesch KA, Dong W, Baker D, Barrett LK, Subramanian S, Samudrala R, Van Voorhis WC. Mycobacterium Cytidylate Kinase Appears to Be an Undruggable Target. J Biomol Screen. 2016; 21(7).
Chopra G, Samudrala R. Exploring Polypharmacology in Drug Discovery and Repurposing Using the CANDO Platform. Curr Pharm Des. 2016; 22(21).
Manocheewa S, Mittler JE, Samudrala R, Mullins JI. Composite Sequence-Structure Stability Models as Screening Tools for Identifying Vulnerable Targets for HIV Drug and Vaccine Development. Viruses. 2015; 7(11).
Matasci N, Hung LH, Yan Z, Carpenter EJ, Wickett NJ, Mirarab S, Nguyen N, Warnow T, Ayyampalayam S, Barker M, Burleigh JG, Gitzendanner MA, Wafula E, Der JP, dePamphilis CW, Roure B, Philippe H, Ruhfel BR, Miles NW, Graham SW, Mathews S, Surek B, Melkonian M, Soltis DE, Soltis PS, Rothfels C, Pokorny L, Shaw JA, DeGironimo L, Stevenson DW, Villarreal JC, Chen T, Kutchan TM, Rolf M, Baucom RS, Deyholos MK, Samudrala R, Tian Z, Wu X, Sun X, Zhang Y, Wang J, Leebens-Mack J, Wong GK. Data access for the 1,000 Plants (1KP) project. Gigascience. 2014; 3.
Hung LH, Samudrala R. fast_protein_cluster: parallel and optimized clustering of large-scale protein modeling data. Bioinformatics. 2014; 30(12).
Redwood CE, Kanvah S, Samudrala R, Saltiel J. Bicycle pedal photoisomerization of 1-phenyl-4-(4-pyridyl)-1,3-butadienes in glassy isopentane at 77 K. Photochem Photobiol Sci. 2013; 12(10).
Laurenzi A, Hung LH, Samudrala R. Structure prediction of partial-length protein sequences. Int J Mol Sci. 2013; 14(7).
Afzal AJ, Srour A, Goil A, Vasudaven S, Liu T, Samudrala R, Dogra N, Kohli P, Malakar A, Lightfoot DA. Homo-dimerization and ligand binding by the leucine-rich repeat domain at RHG1/RFS2 underlying resistance to two soybean pathogens. BMC Plant Biol. 2013; 13.
Martinez-Avila O, Wu S, Kim SJ, Cheng Y, Khan F, Samudrala R, Sali A, Horst JA, Habelitz S. Self-assembly of filamentous amelogenin requires calcium and phosphate: from dimers via nanoribbons to fibrils. Biomacromolecules. 2012; 13(11).
Kota R, Samudrala R, Mattern DL. Synthesis of donor-s-perylenebisimide-acceptor molecules having PEG swallowtails and sulfur anchors. J Org Chem. 2012; 77(21).
Horst JA, Pieper U, Sali A, Zhan L, Chopra G, Samudrala R, Featherstone JD. Strategic protein target analysis for developing drugs to stop dental caries. Adv Dent Res. 2012; 24(2).
Hung LH, Samudrala R. Accelerated protein structure comparison using TM-score-GPU. Bioinformatics. 2012; 28(16).
Moughon SE, Samudrala R. LoCo: a novel main chain scoring function for protein structure prediction based on local coordinates. BMC Bioinformatics. 2011; 12.
Hung LH, Guerquin M, Samudrala R. GPU-Q-J, a fast method for calculating root mean square deviation (RMSD) after optimal superposition. BMC Res Notes. 2011; 4.
Horst OV, Horst JA, Samudrala R, Dale BA. Caries induced cytokine network in the odontoblast layer of human teeth. BMC Immunol. 2011; 12.
Cunningham ML, Horst JA, Rieder MJ, Hing AV, Stanaway IB, Park SS, Samudrala R, Speltz ML. IGF1R variants associated with isolated single suture craniosynostosis. Am J Med Genet A. 2011; 155A(1).
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 Res. 2011; 89(1).
McDermott JE, Corrigan A, Peterson E, Oehmen C, Niemann G, Cambronne ED, Sharp D, Adkins JN, Samudrala R, Heffron F. Computational prediction of type III and IV secreted effectors in gram-negative bacteria. Infect Immun. 2011; 79(1).
Notman R, Oren EE, Tamerler C, Sarikaya M, Samudrala R, Walsh TR. Solution study of engineered quartz binding peptides using replica exchange molecular dynamics. Biomacromolecules. 2010; 11(12).
Wang J, Zhang J, Li R, Zheng H, Li J, Zhang Y, Li H, Ni P, Li S, Li S, Wang J, Liu D, McDermott J, Samudrala R, Liu S, Wang J, Yang H, Yu J, Wong GK. Evolutionary transients in the rice transcriptome. Genomics Proteomics Bioinformatics. 2010; 8(4).
Horst JA, Wang K, Horst OV, Cunningham ML, Samudrala R. Disease risk of missense mutations using structural inference from predicted function. Curr Protein Pept Sci. 2010; 11(7).
Oren EE, Notman R, Kim IW, Evans JS, Walsh TR, Samudrala R, Tamerler C, Sarikaya M. Probing the molecular mechanisms of quartz-binding peptides. Langmuir. 2010; 26(13).
Goldman AD, Samudrala R, Baross JA. The evolution and functional repertoire of translation proteins following the origin of life. Biol Direct. 2010; 5.
Borlee BR, Goldman AD, Murakami K, Samudrala R, Wozniak DJ, Parsek MR. Pseudomonas aeruginosa uses a cyclic-di-GMP-regulated adhesin to reinforce the biofilm extracellular matrix. Mol Microbiol. 2010; 75(4).
Horst J, Samudrala R. Diversity of protein structures and difficulties in fold recognition: the curious case of protein G. F1000 Biol Rep. 2009; 1.
Goldman AD, Leigh JA, Samudrala R. Comprehensive computational analysis of Hmd enzymes and paralogs in methanogenic Archaea. BMC Evol Biol. 2009; 9.
Samudrala R, Heffron F, McDermott JE. Accurate prediction of secreted substrates and identification of a conserved putative secretion signal for type III secretion systems. PLoS Pathog. 2009; 5(4).
Rashid I, McDermott J, Samudrala R. Inferring molecular interactions pathways from eQTL data. Methods Mol Biol. 2009; 541.
Guerquin M, McDermott J, Frazier Z, Samudrala R. The Bioverse API and web application. Methods Mol Biol. 2009; 541.
Frazier Z, McDermott J, Guerquin M, Samudrala R. Computational representation of biological systems. Methods Mol Biol. 2009; 541.
Wichadakul D, McDermott J, Samudrala R. Prediction and integration of regulatory and protein-protein interactions. Methods Mol Biol. 2009; 541.
Jenkins C, Samudrala R, Geary SJ, Djordjevic SP. Structural and functional characterization of an organic hydroperoxide resistance protein from Mycoplasma gallisepticum. J Bacteriol. 2008; 190(6).
Ngan SC, Hung LH, Liu T, Samudrala R. Scoring functions for de novo protein structure prediction revisited. Methods Mol Biol. 2008; 413.
Jenwitheesuk E, Samudrala R. Identification of potential HIV-1 targets of minocycline. Bioinformatics. 2007; 23(20).
Chevance FF, Takahashi N, Karlinsey JE, Gnerer J, Hirano T, Samudrala R, Aizawa S, Hughes KT. The mechanism of outer membrane penetration by the eubacterial flagellum and implications for spirochete evolution. Genes Dev. 2007; 21(18).
Berube PM, Samudrala R, Stahl DA. Transcription of all amoC copies is associated with recovery of Nitrosomonas europaea from ammonia starvation. J Bacteriol. 2007; 189(11).
Wang K, Samudrala R. Incorporating background frequency improves entropy-based residue conservation measures. BMC Bioinformatics. 2006; 7.
Korotkova N, Le Trong I, Samudrala R, Korotkov K, Van Loy CP, Bui AL, Moseley SL, Stenkamp RE. Crystal structure and mutational analysis of the DaaE adhesin of Escherichia coli. J Biol Chem. 2006; 281(31).
Howell DP, Samudrala R, Smith JD. Disguising itself--insights into Plasmodium falciparum binding and immune evasion from the DBL crystal structure. Mol Biochem Parasitol. 2006; 148(1).
Ngan SC, Inouye MT, Samudrala R. A knowledge-based scoring function based on residue triplets for protein structure prediction. Protein Eng Des Sel. 2006; 19(5).
Chang AN, McDermott J, Frazier Z, Guerquin M, Samudrala R. INTEGRATOR: interactive graphical search of large protein interactomes over the Web. BMC Bioinformatics. 2006; 7.
Liu T, Jenwitheesuk E, Teller DC, Samudrala R. Structural insights into the cellular retinaldehyde-binding protein (CRALBP). Proteins. 2005; 61(2).
Chang AN, McDermott J, Samudrala R. An enhanced Java graph applet interface for visualizing interactomes. Bioinformatics. 2005; 21(8).
Jenwitheesuk E, Samudrala R. Virtual screening of HIV-1 protease inhibitors against human cytomegalovirus protease using docking and molecular dynamics. AIDS. 2005; 19(5).
Yu J, Wang J, Lin W, Li S, Li H, Zhou J, Ni P, Dong W, Hu S, Zeng C, Zhang J, Zhang Y, Li R, Xu Z, Li S, Li X, Zheng H, Cong L, Lin L, Yin J, Geng J, Li G, Shi J, Liu J, Lv H, Li J, Wang J, Deng Y, Ran L, Shi X, Wang X, Wu Q, Li C, Ren X, Wang J, Wang X, Li D, Liu D, Zhang X, Ji Z, Zhao W, Sun Y, Zhang Z, Bao J, Han Y, Dong L, Ji J, Chen P, Wu S, Liu J, Xiao Y, Bu D, Tan J, Yang L, Ye C, Zhang J, Xu J, Zhou Y, Yu Y, Zhang B, Zhuang S, Wei H, Liu B, Lei M, Yu H, Li Y, Xu H, Wei S, He X, Fang L, Zhang Z, Zhang Y, Huang X, Su Z, Tong W, Li J, Tong Z, Li S, Ye J, Wang L, Fang L, Lei T, Chen C, Chen H, Xu Z, Li H, Huang H, Zhang F, Xu H, Li N, Zhao C, Li S, Dong L, Huang Y, Li L, Xi Y, Qi Q, Li W, Zhang B, Hu W, Zhang Y, Tian X, Jiao Y, Liang X, Jin J, Gao L, Zheng W, Hao B, Liu S, Wang W, Yuan L, Cao M, McDermott J, Samudrala R, Wang J, Wong GK, Yang H. The Genomes of Oryza sativa: a history of duplications. PLoS Biol. 2005; 3(2).
Jenwitheesuk E, Samudrala R. Heptad-repeat-2 mutations enhance the stability of the enfuvirtide-resistant HIV-1 gp41 hairpin structure. Antivir Ther. 2005; 10(8).
Jenwitheesuk E, Samudrala R. Prediction of HIV-1 protease inhibitor resistance using a protein-inhibitor flexible docking approach. Antivir Ther. 2005; 10(1).
Ekwa-Ekoka C, Diaz GA, Carlson C, Hasegawa T, Samudrala R, Lim KC, Yabu JM, Levy B, Schnapp LM. Genomic organization and sequence variation of the human integrin subunit alpha8 gene (ITGA8). Matrix Biol. 2004; 23(7).
Wang K, Jenwitheesuk E, Samudrala R, Mittler JE. Simple linear model provides highly accurate genotypic predictions of HIV-1 drug resistance. Antivir Ther. 2004; 9(3).
Jenwitheesuk E, Samudrala R. Identifying inhibitors of the SARS coronavirus proteinase. Bioorg Med Chem Lett. 2003; 13(22).
McDermott J, Samudrala R. Bioverse: Functional, structural and contextual annotation of proteins and proteomes. Nucleic Acids Res. 2003; 31(13).
Hung LH, Samudrala R. PROTINFO: Secondary and tertiary protein structure prediction. Nucleic Acids Res. 2003; 31(13).
Hung LH, Samudrala R. Accurate and automated classification of protein secondary structure with PsiCSI. Protein Sci. 2003; 12(2).
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 bacterial genus Prosthecobacter. Proc Natl Acad Sci U S A. 2002; 99(26).
Van Loy CP, Sokurenko EV, Samudrala R, Moseley SL. Identification of amino acids in the Dr adhesin required for binding to decay-accelerating factor. Mol Microbiol. 2002; 45(2).
Samudrala R, Levitt M. Decoys 'R' Us: a database of incorrect conformations to improve protein structure prediction. Protein Sci. 2000; 9(7).
Xia Y, Huang ES, Levitt M, Samudrala R. Ab initio construction of protein tertiary structures using a hierarchical approach. J Mol Biol. 2000; 300(1).
Huang ES, Samudrala R, Park BH. Scoring functions for ab initio protein structure prediction. Methods Mol Biol. 2000; 143.
Samudrala R, Xia Y, Levitt M, Huang ES. A combined approach for ab initio construction of low resolution protein tertiary structures from sequence. Pac Symp Biocomput. 1999.
Samudrala R, Moult J. Determinants of side chain conformational preferences in protein structures. Protein Eng. 1998; 11(11).
Huang ES, Samudrala R, Ponder JW. Distance geometry generates native-like folds for small helical proteins using the consensus distances of predicted protein structures. Protein Sci. 1998; 7(9).

See all (74 more)

Presentations:

"Interactomics: Computational Analysis of Novel Drug Opportunities. International conference on Clinical Sciences and Drug Discovery." (2015)
"Multiscale modelling of relationships between protein classes and drug behavior across all diseases using the cando platform." International Conference on Protein Engineering (2015)
"Interactome based drug discovery. Intelligent Systems in Molecular Biology." (2015)
"Interactomics: Computational Analysis of Novel Drug Opportunities. Significant Advances in Bioengineering." (2015)
"Interactomics: Computational Analysis of Novel Drug Opportunities. NIH Common Fund High-Risk High-Reward Symposium." (2014)
"Interactomics: Computational Analysis of Novel Drug Opportunities." , Michael Levitt Nobel Memorial Symposium (2014)
"Interactomics: Computational Analysis of Novel Drug Opportunities. Systems Biology of Infectious Diseases" (2014)
"Interactomics: Computational Analysis of Novel Drug Opportunities. Intelligent Systems in Molecular Biology" (2014)
"Interactomics: Atomic systems biology translated to drug discovery. From High-throughput Structural Bioinformatics to Integrative Systems Biology" Network Tools and Applications in Biology Conference

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Contact Information

77 Goodell St
Gateway Building
Buffalo, NY 14203
Phone: 716-888-4858
Email: rams@buffalo.edu

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