Biochemistry, Biophysics, and Structural Biology Commons^™

Arabinose Substitution Effect On Xylan Rigidity And Self-Aggregation, Utsab Shrestha, Sydney Smith, Sai Venkatesh Pingali, Hui Yang, Mai Zahran, Llyod Breunig, Liza Wilson, Daniel Cosgrove, Hugh O'Neill, Loukas Petridis

Publications and Research

Substituted xylans play an important role in the structure and mechanics of the primary cell wall of plants. Arabinoxylans (AX) consist of a xylose backbone substituted with arabinose, while glucuronoarabinoxylans (GAX) also contain glucuronic acid substitutions and ferulic acid esters on some of the arabinoses. We provide a molecular-level description on the dependence of xylan conformational, selfaggregation properties and binding to cellulose on the degree of arabinose substitution. Molecular dynamics simulations reveal fully solubilized xylans with a low degree of arabinose substitution (lsAX) to be stiffer than their highly substituted (hsAX) counterparts. Small-angle neutron scattering experiments indicate that both wild-type …

Ribosomally Synthesized And Post-Translationally Modified Peptides As Potential Scaffolds For Peptide Engineering, Devan Bursey

Theses and Dissertations

Peptides are small proteins that are crucial in many biological pathways such as antimicrobial defense, hormone signaling, and virulence. They often exhibit tight specificity for their targets and therefore have great therapeutic potential. Many peptide-based therapeutics are currently available, and the demand for this type of drug is expected to continue to increase. In order to satisfy the growing demand for peptide-based therapeutics, new engineering approaches to generate novel peptides should be developed. Ribosomally synthesized and post-translationally modified peptides (RiPPs) are a group of peptides that have the potential to be effective scaffolds for in vivo peptide engineering projects. These …

Transition State Interactions In A Promiscuous Enzyme: Sulfate And Phosphate Monoester Hydrolysis By Pseudomonas Aeruginosa Arylsulfatase, Bert Van Loo, Ryan Berry, Usa Boonyuen, Mark F. Mohamed, Marko Golicnik, Alvan C. Hengge, Florian Hollfelder

Chemistry and Biochemistry Faculty Publications

Pseudomonas aeruginosa arylsulfatase (PAS) hydrolyses sulfate and, promiscuously, phosphate monoesters. Enzyme-catalyzed sulfate transfer is crucial to a wide variety of biological processes, but detailed studies of the mechanistic contributions to its catalysis are lacking. We present linear free energy relationships (LFERs) and kinetic isotope effects (KIEs) of PAS and active site mutants that suggest a key role for leaving group (LG) stabilization. In LFERs PAS^_WT has a much less negative Brønsted coefficient (ß_{leaving group} ^obs-Enz=-0.33) than the uncatalyzed reaction (ß_{leaving group} ^obs=-1.81). This situation is diminished when cationic active site groups are exchanged for alanine. …

Long-Term, Super-Resolution Imaging Of Amyloid Structures Using Transient Amyloid Binding Microscopy, Tianben Ding, Kevin Spehar, Jan Bieschke, Matthew D. Lew

Electrical & Systems Engineering Publications and Presentations

Amyloid fibrils and tangles are signatures of Alzheimer disease, but nanometer-sized aggregation intermediates are hypothesized to be the structures most toxic to neurons. The structures of these oligomers are too small to be resolved by conventional light microscopy. We have developed a simple and versatile method, called transient amyloid binding (TAB), to image amyloid structures with nanoscale resolution using amyloidophilic dyes, such as Thioflavin T, without the need for covalent labeling or immunostaining of the amyloid protein. Transient binding of ThT molecules to amyloid structures over time generates photon bursts that are used to localize single fluorophores with nanometer precision. …

Autophagic Flux Modulation By Wnt/Β-Catenin Pathway Inhibition In Hepatocellular Carcinoma, Lilia Turcios, Heather E. Chacon, Catherine Garcia, Pedro Eman, Virgilius Cornea, Jieyun Jiang, Brett T. Spear, Chunming Liu, David S. Watt, Francesc Marti, Roberto Gedaly

Surgery Faculty Publications

Autophagy targets cellular components for lysosomal-dependent degradation in which the products of degradation may be recycled for protein synthesis and utilized for energy production. Autophagy also plays a critical role in cell homeostasis and the regulation of many physiological and pathological processes and prompts this investigation of new agents to effect abnormal autophagy in hepatocellular carcinoma (HCC). 2,5-Dichloro-N-(2-methyl-4-nitrophenyl) benzenesulfonamide (FH535) is a synthetic inhibitor of the Wnt/β-catenin pathway that exhibits anti-proliferative and anti-angiogenic effects on different types of cancer cells. The combination of FH535 with sorafenib promotes a synergistic inhibition of HCC and liver cancer stem cell proliferation, …

Allosteric Mechanism Of The Circadian Protein Vivid Resolved Through Markov State Model And Machine Learning Analysis, Hongyu Zhou, Zheng Dong, Gennady M. Verkhivker, Brian D. Zoltowski, Peng Tao

Mathematics, Physics, and Computer Science Faculty Articles and Research

The fungal circadian clock photoreceptor Vivid (VVD) contains a photosensitive allosteric light, oxygen, voltage (LOV) domain that undergoes a large N-terminal conformational change. The mechanism by which a blue-light driven covalent bond formation leads to a global conformational change remains unclear, which hinders the further development of VVD as an optogenetic tool. We answered this question through a novel computational platform integrating Markov state models, machine learning methods, and newly developed community analysis algorithms. Applying this new integrative approach, we provided a quantitative evaluation of the contribution from the covalent bond to the protein global conformational change, and proposed an …

Coupling Of Parp1-Mediated Chromatin Structural Changes To Transcriptional Rna Polymerase Ii Elongation And Cotranscriptional Splicing, Elena A. Matveeva, Qamar M. H. Al-Tinawi, Eric C. Rouchka, Yvonne N. Fondufe-Mittendorf

Molecular and Cellular Biochemistry Faculty Publications

Background: Recently, we showed that PARP1 is involved in cotranscriptional splicing, possibly by bridging chromatin to RNA and recruiting splicing factors. It also can influence alternative splicing decisions through the regulation of RNAPII elongation. In this study, we investigated the effect of PARP1-mediated chromatin changes on RNAPII movement, during transcription and alternative splicing.

Results: We show that RNAPII pauses at PARP1–chromatin structures within the gene body. Knockdown of PARP1 abolishes this RNAPII pausing, suggesting that PARP1 may regulate RNAPII elongation. Additionally, PARP1 alters nucleosome deposition and histone post-translational modifications at specific exon–intron boundaries, thereby affecting RNAPII movement. Lastly, genome-wide analyses …

Rna Sequencing, Selection Of Reference Genes And Demonstration Of Feeding Rnai In Thrips Tabaci (Lind.) (Thysanoptera: Thripidae), Satnam Singh, Mridula Gupta, Suneet Pandher, Gurmeet Kaur, Neha Goel, Pankaj Rathore, Subba Reddy Palli

Entomology Faculty Publications

Background: Thrips tabaci is a severe pest of onion and cotton. Due to lack of information on its genome or transcriptome, not much is known about this insect at the molecular level. To initiate molecular studies in this insect, RNA was sequenced; de novo transcriptome assembly and analysis were performed. The RNAseq data was used to identify reference and RNAi pathway genes in this insect. Additionally, feeding RNAi was demonstrated in T. tabaci for the first time.

Results: From the assembled transcriptome, 27,836 coding sequence (CDS) with an average size of 1236 bp per CDS were identified. About 85.4% of …

Using Publicly Available Genbank Data To Teach Plant Phylogeny In High School Classrooms, Madhav P. Nepal, Ethan J. Andersen

iLEARN Teaching Resources

In this teaching module, students will learn about NCBI GenBank, search for DNA/protein sequences from multiple plant species of a gene that encodes Rubisco enzyme, construct and interpret a phylogenetic tree, and discuss traits that allowed plants to adapt their life on land.

Student-Faculty Collaborative Research Grant Report, Megan Bestwick

Post-Grant Reports

Mitochondria are essential organelles in most eukaryotic cells because of their role in metabolism and the production of ATP by the oxidative phosphorylation (OXPHOS) pathway, as well as other key cellular processes. Metal cofactors, such as copper (Cu) and iron (Fe), are incorporated into OXPHOS protein complexes of yeast located within the inner membrane of the mitochondria. Misincorporation or modulation of these available metals in mitochondrial enzymes leads to the production of reactive oxygen species (ROS). ROS are reactive molecules containing oxygen such as peroxides, superoxide, and hydroxyl radicals. Yeast are a good model for studying aging and the effect …

Clinical Features, Survival And Prognostic Factors Of Glycogen-Rich Clear Cell Carcinoma (Grcc) Of The Breast In The U.S. Population, Zhengqiu Zhou, Connor J. Kinslow, Hanina Hibshoosh, Hua Guo, Simon K. Cheng, Chunyan He, Matthew S. Gentry, Ramon C. Sun

Molecular and Cellular Biochemistry Faculty Publications

The World Health Organization (WHO) defines glycogen-rich clear cell carcinoma (GRCC) of the breast as a carcinoma with glycogen accumulation in more than 90% of its tumor cells. Due to the rarity of this disease, its reported survival and clinical associations have been inconsistent due to reliance on case reports and limited case series. As a result, the prognostic implication of this cancer subtype remains unclear. Using the U.S. Surveillance, Epidemiology, and End Results (SEER) program database, we compared the incidence, demographics and prognostic factors of 155 cases of GRCC of the breast to 1,251,584 cases of other (non-GRCC) breast …

Induction Of Met Receptor Tyrosine Kinase Down-Regulation Through Antibody-Mediated Receptor Clustering, Wenjing Li, Adam Dick, Fei Lu, Hong Sun

Chemistry and Biochemistry Faculty Research

The proto-oncoprotein MET is a receptor tyrosine kinase that plays a key role in cancer cell growth and invasion. We have used fluorescence-tagged antibodies to activate MET in live serum-starved glioblastoma cells and monitor the fate of antibody-bound MET receptor in single cell-based assays. We found that the antibodies induced rapid and transient formation of highly polarized MET clusters on the plasma membrane and promoted the activation of MET, resembling the initial effects of binding to its ligand, HGF. However, the antibody-induced clustering and activation of MET led to the rapid removal of the receptor from cell surface and altered …

A New Multivariate Optical Computing Microelement And Miniature Sensor For Spectroscopic Chemical Sensing In Harsh Environments: Design, Fabrication, And Testing, Christopher M. Jones, Bin Dai, Jimmy Price, Jian Li, Megan Pearl, Bill Soltmann, Michael L. Myrick

Faculty Publications

Multivariate optical computing (MOC) is a compressed sensing technique with the ability to provide accurate spectroscopic compositional analysis in a variety of different applications to multiple industries. Indeed, recent developments have demonstrated the successful deployment of MOC sensors in downhole/well-logging environments to interrogate the composition of hydrocarbon and other chemical constituents in oil and gas reservoirs. However, new challenges have necessitated sensors that operate at high temperatures and pressures (up to 230 °C and 138 MPa) as well as even smaller areas that require the miniaturization of their physical footprint. To this end, this paper details the design, fabrication, and …

Starvation Resistance Is Associated With Developmentally Specified Changes In Sleep, Feeding And Metabolic Rate, Elizabeth B. Brown, Melissa E. Slocumb, Milan Szuperak, Arianna Kerbs, Allen G. Gibbs, Matthew S. Kayser, Alex C. Keene

Life Sciences Faculty Research

Food shortage represents a primary challenge to survival, and animals have adapted diverse developmental, physiological and behavioral strategies to survive when food becomes unavailable. Starvation resistance is strongly influenced by ecological and evolutionary history, yet the genetic basis for the evolution of starvation resistance remains poorly understood. The fruit fly Drosophila melanogaster provides a powerful model for leveraging experimental evolution to investigate traits associated with starvation resistance. While control populations only live a few days without food, selection for starvation resistance results in populations that can survive weeks. We have previously shown that selection for starvation resistance results in increased …

Transition State Analysis Of The Reaction Catalyzed By The Phosphotriesterase From Sphingiobium Sp. Tcm1, Andrew N. Bigley, Dao Feng Xiang, Tamari Narindoshvili, Charlie W. Burgert, Alvan C. Hengge, Frank M. Raushel

Chemistry and Biochemistry Faculty Publications

Organophosphorus flame retardants are stable toxic compounds used in nearly all durable plastic products and are considered major emerging pollutants. The phosphotriesterase from Sphingobium sp. TCM1 (Sb-PTE) is one of the few enzymes known to be able to hydrolyze organophosphorus flame retardants such as triphenyl phosphate and tris(2-chloroethyl) phosphate. The effectiveness of Sb-PTE for the hydrolysis of these organophosphates appears to arise from its ability to hydrolyze unactivated alkyl and phenolic esters from the central phosphorus core. How Sb-PTE is able to catalyze the hydrolysis of the unactivated substituents is not known. To interrogate the catalytic …

Exposure Characterization Of Haloacetic Acids In Humans For Exposure And Risk Assessment Applications: An Exploratory Study, Shahid Parvez, Jeffrey L. Ashby, Susana Y. Kimura, Susan D. Richardson

Faculty Publications

Disinfected water is the major source of haloacetic acids (HAAs) in humans, but their inter- and intra-individual variability for exposure and risk assessment applications is under-researched. Thus, we measured HAAs in cross-sectional and longitudinal urine and water specimens from 17 individuals. Five regulated HAAs—mono-, di-, and trichloroacetic acid (MCAA, DCAA, and TCAA) and mono- and dibromoacetic acid (MBAA and DBAA)—and one unregulated HAA—bromochloroacetic acid (BCAA)—were measured. Urinary DCAA, MBAA, DBAA, and BCAA levels were always below the limits of detection (LOD). Measured levels and interindividual variability of urinary MCAA were higher than urinary TCAA. Longitudinal urinary specimens showed MCAA levels …

Evaluation Of Volatile Metabolites Emitted In-Vivo From Cold-Hardy Grapes During Ripening Using Spme And Gc-Ms: A Proof-Of-Concept, Somchai Rice, Devin L. Maurer, Anne Fennell, Murlidhar Dharmadhikari, Jacek A. Koziel

Agronomy, Horticulture and Plant Science Faculty Publications

In this research, we propose a novel concept for a non-destructive evaluation of volatiles emitted from ripening grapes using solid-phase microextraction (SPME). This concept is novel to both the traditional vinifera grapes and the cold-hardy cultivars. Our sample models are cold-hardy varieties in the upper Midwest for which many of the basic multiyear grape flavor and wine style data is needed. Non-destructive sampling included a use of polyvinyl fluoride (PVF) chambers temporarily enclosing and concentrating volatiles emitted by a whole cluster of grapes on a vine and a modified 2 mL glass vial for a vacuum-assisted sampling of volatiles from …

Interaction And Regulation Between Lipid Mediator Phosphatidic Acid And Circadian Clock Regulators, Sang-Chul Kim, Sang-Chul Kim, Dmitri Nusinow, Maria Sorkin, Maria Sorkin, Jose Pruneda-Paz, Xuemin Wang, Xuemin Wang

Biology Department Faculty Works

Circadian clocks play important roles in regulating cellular metabolism, but the reciprocal effect that metabolism has on the clock is largely unknown in plants. Here we show that the central glycerolipid metabolite and lipid mediator phosphatidic acid (PA) interacts with and modulates the function of the core clock regulators LATE ELONGATED HYPOCOTYL (LHY) and CIRCADIAN CLOCK ASSOCIATED1 (CCA1) in Arabidopsis thaliana. PA reduced the ability of LHY and CCA1 to bind the promoter of their target gene TIMING OF CAB EXPRESSION1. Increased PA accumulation and inhibition of PA-producing enzymes had opposite effects on circadian clock outputs. Diurnal change in levels …

Composition Of The Survival Motor Neuron (Smn) Complex In Drosophila Melanogaster, A. Gregory Matera, Amanda C. Raimer, Casey A. Schmidt, Jo A. Kelly, Gaith N. Droby, David Baillat, Sara Ten Have, Angus I. Lamond, Eric J. Wagner, Kelsey M. Gray

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Spinal Muscular Atrophy (SMA) is caused by homozygous mutations in the human survival motor neuron 1 (SMN1) gene. SMN protein has a well-characterized role in the biogenesis of small nuclear ribonucleoproteins (snRNPs), core components of the spliceosome. SMN is part of an oligomeric complex with core binding partners, collectively called Gemins. Biochemical and cell biological studies demonstrate that certain Gemins are required for proper snRNP assembly and transport. However, the precise functions of most Gemins are unknown. To gain a deeper understanding of the SMN complex in the context of metazoan evolution, we investigated its composition in Drosophila …

Solvation Thermodynamic Mapping In Computer Aided Drug Design, Steven Ramsey

Dissertations, Theses, and Capstone Projects

The displacement of water from surfaces upon biomolecular recognition and association makes a significant contribution to the free energy changes of these processes. We therefore posit that accurate characterization of local structural and thermodynamic molecular water properties can improve computational model accuracy and predictivity of recognition and association processes. In this thesis, we discuss Solvation Thermodynamic Mapping (STM) methods that we have developed using inhomogeneous fluid solvation theory (IST) to better characterize active site water structural and thermodynamic properties on protein surfaces and the open source tools that we have developed, GIST-CPPTRAJ and SSTMap, which implement these methods which we …

The Determining Factors Of The Self-Assembly Of Collagen Mimetic Peptide, Fangfang Chen

Dissertations, Theses, and Capstone Projects

We recently reported that a designed triple helix Col108 self-associates to form collagen-like mini-fibrils having a d-periodicity of 35 nm. Recombinant protein Col108 consists of 378-residue triple helix domain organized into three repeating sequence units, and a C-terminal foldon domain. The 35 nm d-period of Col108 mini-fibrils is consistent with the one unit staggered arrangement of the associating helices. To further investigate if the sequence periodicity is crucial for collagen mimetic peptide fibril formation, we studied the self-assembly of four other designed triple helical peptides. Peptide 2U108 has two repeating sequence units; peptide Col877 consists of three repeating …

Pretargeted Radioimmunotherapy Utilizing The Inverse Electron Demand Diels-Alder Reaction, Rosemery Membreno

Dissertations, Theses, and Capstone Projects

Radioimmunotherapy capitalizes on the specificity and affinity of antibodies for their antigens to localize radioactivity at the tumor site. One limitation in using antibodies is their long circulation time, which can take days to weeks to fully clear from blood circulation. When a radioisotope is directly conjugated to this immunoglobulin vector, the red marrow and other healthy organs are receiving a constant radiation dose while it is in blood circulation. This not only harms healthy organs, but limits the dose of radioactivity that can be administered thus prolonging treatment. A promising alternative to limit the radiation dose to non-tumor tissue …

Bisthioether Stapled Peptides Targeting Polycomb Repressive Complex 2 Gene Repression, Gan Zhang

Dissertations, Theses, and Capstone Projects

Interactions between proteins play a key role in nearly all cellular process, and therefore, disruption of such interactions may lead to many different types of cellular dysfunctions. Hence, pathologic protein-protein interactions (PPIs) constitute highly attractive drug targets and hold great potential for developing novel therapeutic agents for the treatment of incurable human diseases. Unfortunately, the identification of PPI inhibitors is an extremely challenging task, since traditionally used small molecule ligands are mostly unable to cover and anchor on the extensive flat surfaces that define those binary protein complexes. In contrast, large biomolecules such as proteins or peptides are ideal fits …

Ck2 Negatively Regulates 5-Ht4 Receptor Signaling In The Prefrontal Cortex And Mediates Depression-Like Behaviors, Julia Castello Saval

Dissertations, Theses, and Capstone Projects

The serotonergic system has been the major candidate in the pathophysiology of mood related disorders such as anxiety and major depressive disorder (MDD). Unfortunately, current antidepressant drugs are ineffective in 50% of the population and require chronic administration for a period of 3-6 weeks before the onset of therapeutic response. 5-HT4 receptor (5-HT₄R) agonists have emerged as potential candidates for fast antidepressant action, since an antidepressant response can be achieved after 3 days of pharmacological administration in rodents.

This dissertation aims to investigate the role of casein kinase 2 (CK2) as a regulator of 5-HT₄R expression …

Analysis Of Oxygen-18 Labeled Phosphate To Study Positional Isotope Experiments Using Lc-Qtof-Ms, Sujatha Chilakala, Iteen Cheng, Ireen Lee, Yan Xu

Chemistry Faculty Publications

A method is proposed in this paper for the determination of oxygen-18 labeled phosphate so that positional isotope experiments using sensitive and rapid liquid chromatography–QTOF–mass spectrometry (LC-QTOF-MS) experiments can be carried out. The positional isotope exchange technique is a useful tool in understanding the mechanisms and kinetics of many enzyme-catalyzed reactions. Detection of the positions and concentration of these exchanged isotopes is the key. Gas chromatography–mass spectrometry (GC-MS) and nuclear magnetic resonance imaging are commonly used analytical techniques for measurement of ¹⁸O/¹⁶O, ³¹P and ¹⁵N isotope enrichment. Since these techniques either require a time-consuming derivatization …

Lncegfl7os Regulates Human Angiogenesis By Interacting With Max At The Egfl7/Mir-126 Locus, Quinbo Zhou, Chastain Anderson, Zhan-Peng Huang, Jakub Hanus, Wensheng Zhang, Yu Han

Faculty and Staff Publications

In an effort to identify human endothelial cell (EC)-enriched lncRNAs,~500 lncRNAswere shown to be highly restricted in primary human ECs. Among them,lncEGFL7OS, located inthe opposite strand of theEGFL7/miR-126gene, is regulated by ETS factors through abidirectional promoter in ECs. It is enriched in highly vascularized human tissues, and upregulatedin the hearts of dilated cardiomyopathy patients. LncEGFL7OS silencing impairs angiogenesis asshown by EC/fibroblast co-culture, in vitro/in vivo and ex vivo human choroid sproutingangiogenesis assays, while lncEGFL7OS overexpression has the opposite function. Mechanistically,lncEGFL7OS is required for MAPK and AKT pathway activation by regulating EGFL7/miR-126expression. MAX protein was identified as a lncEGFL7OS-interacting protein that …

Characterization Of Immunomodulatory Microbial Factors In Medicinal Plants, Kriti Kalpana

Dissertations, Theses, and Capstone Projects

Medicinal plants are one of the biggest sources of natural products with therapeutic importance. There are currently over 28,000 plants with putative medicinal values. Plant-derived compounds have been explored extensively for various biological activities ranging from anti-cancer, immune-boosting to anti-inflammatory and anti-oxidant. Some of the most important therapeutic agents are of plant-origin, such as paclitaxel from Pacific yew (Taxus brevifolia) and artemisinin from qinghao su (a Chinese medicinal herb; a.k.a. Artemisia annua) to name a few.

The study presented in this thesis started out as classical pharmacognosy research, which focused on the identification of immunostimulatory factors in …

Structural Studies On Calcium/Calmodulin-Dependent Activation Of Eukaryotic Elongation Factor 2 Kinase, Kwangwoon Lee

Dissertations, Theses, and Capstone Projects

Eukaryotic elongation factor 2 kinase (eEF-2K) is a key modulator of the rate of protein synthesis. Activated by calcium-loaded calmodulin (Ca²⁺-CaM), eEF-2K phosphorylates its only known physiological substrate, eEF-2, on a specific threonine residue (Thr-56). Phosphorylated eEF-2 has reduced affinity for the ribosome, and results in a significant decrease in the rate of translation elongation. Modulation of the rate of translation elongation plays a crucial role in proteostasis – adequate regulation of protein synthesis, protein folding, and protein degradation that greatly influences cellular growth and survival. Binding of Ca²⁺-CaM triggers activation of eEF-2K and remains intact …

The Effect Of Dynamic Kinetic Selection On An Evolving Ribozyme Population, Patrick David Poletti

Dissertations and Theses

Dynamic Kinetic Selection (DKS) suggests that kinetic, rather than thermodynamic, stability will dictate the composition of a replicating population of biomolecules. Here, the results obtained from a series of five related reactions involving gradually increasing percentages of randomly-mutated substrate fragments to generate variants of full-length Azoarcus group I intron through an autocatalytic self-assembly reaction involving a series of recombination events, showed DKS as a driving factor in dictating the population composition of full-length product assembled from substrates that had fewer positions available to randomization.

In trying to elucidate a plausible scheme for the origins of complex biomolecules on the prebiotic …

A Rational Approach For Creating Peptides Mimicking Antibody Binding, Sameer Sachdeva, Hyun Joo, Jerry Tsai, Bhaskara Jasti, Xiaoling Li

School of Pharmacy Faculty Articles

This study reports a novel method to design peptides that mimic antibody binding. Using the Knob-Socket model for protein-protein interaction, the interaction surface between Cetuximab and EGFR was mapped. EGFR binding peptides were designed based on geometry and the probability of the mapped knob-sockets pairs. Designed peptides were synthesized and then characterized for binding specificity, affinity, cytotoxicity of drug-peptide conjugate and inhibition of phosphorylation. In cell culture studies, designed peptides specifically bind and internalize to EGFR overexpressing cells with three to four-fold higher uptake compared to control cells that do not overexpress EGFR. The designed peptide, Pep11, bound to EGFR …