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What X-Ray Diffraction & Crystallography got wrong, from 51 theses
Summary written by a model from the records below: The records describe numerous technical obstacles encountered during macromolecular and small-molecule X-ray crystallography as well as powder diffraction experiments. Investigators frequently reported failed crystallization, poor diffraction resolution, refinement divergence due to peak overlap, and limits in detecting disordered or weakly scattering phases. These records come from graduate theses, 2021 to 2026, each labeled with its degree where the repository states it, and each links to its thesis. They were extracted by language models reading the full text, so treat each as a lead to read, not a verdict.
Plus 9 problems the authors left open, listed at the end.
Failure modes, by theses reporting them
Select a mode to jump to its records.
Macromolecular crystal diffraction degrades or fails due to crystal damage and lattice disruption
Macromolecular crystals frequently yielded weak or unindexable diffraction patterns and suffered lattice degradation from cryoprotectant or ligand soaking. In addition, experimental workflows were impeded by crystal desiccation, radiation damage, or ice crystal formation during harvesting.
Tried and failed
X-ray crystallography and cryo-EM structure determination applied to heteromeric restriction modification protein complexes. Outcome: no signal. Reason: Structural determination attempts failed to resolve the multiprotein complex architectures
INVESTIGATING THE EVOLUTION OF NUCLEOTIDE SPECIFICITY AND ORGANIZATION OF DNA BINDING IN MCRBC COMPLEXES · Cornell · PhD
Tried and failed
X-ray crystallography of large macromolecular complexes applied to full-length protein-RNA initiation complex. Outcome: no signal. Reason: Crystals failed to produce measurable X-ray diffraction
Structural Understanding of Remodeling Function of HIV-1 Reverse Transcriptase During Initiation · Harvard · PhD
Tried and failed
macromolecular X-ray crystallography applied to protein-RNA complex. Reason: crystals exhibited multiple unindexable diffraction lattices
Structural Understanding of Remodeling Function of HIV-1 Reverse Transcriptase During Initiation · Harvard · PhD
Tried and failed
post-crystallization soaking with standard cryoprotectants applied to protein crystals for X-ray diffraction. Reason: cryoprotectant soaking degraded crystal quality, causing low-resolution streaking diffraction
Structural Insights into Mycobacteriales Galactan Biosynthesis · MIT · PhD
Tried and failed
X-ray crystallography on heterooligomeric protein complexes applied to recombinant collagen C-propeptide heterotrimers. Outcome: no signal. Reason: crystals diffracted weakly and to low resolution, preventing space group assignment and structure determination
Structural and biochemical investigations of collagen-I trimerization · MIT · PhD
Tried and failed
fragment co-crystallization and soaking for X-ray crystallography applied to methyltransferase protein-ligand complex structure determination. Outcome: no signal. Reason: fragment screening hits failed to yield co-crystal structures via soaking or co-crystallization
Development and evaluation of potential co-factor competitive inhibitors for the histone lysine methyltransferase G9a · Imperial · PhD
Tried and failed
Ligand soaking and co-crystallization applied to protein crystal structure determination. Outcome: unstable. Reason: Ligand binding disrupted crystal packing, causing loss of X-ray diffraction
Characterization and targeting of the 2-methylcitrate cycle in Pseudomonas aeruginosa · Cambridge · PhD
Tried and failed
Protein X-ray crystallography applied to mutant protein structure determination. Reason: cysteine residues formed an artifactual intermolecular disulfide bond during crystal packing
Covalent Inhibition of Pro-Apoptotic BAX · Harvard · PhD
Considered and rejected
Considered and rejected: Shelved X-ray crystallography of the RecA3x-LexA complex after initial hits failed to yield interpretable diffraction due to ice crystal formation during harvesting, pivoting entirely to cryo-EM
BIOCHEMICAL AND STRUCTURAL ANALYSIS OF THE SOS SIGNAL COMPLEX · Penn · PhD
Considered and rejected
Considered and rejected: Abandoned X-ray crystallography attempts due to reproducibility and diffraction issues, shifting structural efforts entirely to single-particle Cryo-EM.
Structural determination of Entamoeba Histolytica TGT and its binding to tRNAASP · Leibniz Universität Hannover · PhD
Considered and rejected
Considered and rejected: Abandoned X-ray crystallography optimization after initial 23Å diffraction in favor of single-particle cryo-EM due to poor protein yields and faster iteration cycles.
Considered and rejected
Considered and rejected: Abandoned optimization of Ura7 X-ray crystallization after crystal structure resolved in the inactive conformation despite substrate presence.
Structure and Function of the Yeast Metabolic Filament CTP Synthase · University of Washington · PhD
Tried and failed
room-temperature single-crystal X-ray diffraction applied to light-sensitive protein crystals. Outcome: unstable. Reason: rapid dehydration, radiation damage, and poor diffraction quality under ambient conditions
Understanding Light-Regulation by CRYPTOCHROME: A Structural Story · Cornell · PhD
Conformational flexibility and structural heterogeneity prevent macromolecular crystal formation
Target proteins containing flexible termini, disordered loops, or destabilizing mutations failed to produce crystals across extensive screening conditions. Structural heterogeneity such as variable oligomerization, low solubility, and aberrant disulfide crosslinking further inhibited the growth of diffraction-quality crystals.
Tried and failed
X-ray crystallography applied to engineered protein loop deletion mutants. Outcome: no signal. Reason: Crystals could not be obtained or diffraction data failed to resolve structure
Elucidating novel chemical and genetic mechanisms of LSD1-HDAC1/2-CoREST complex regulation · Harvard · PhD
Tried and failed
X-ray crystallography applied to destabilized protein variants. Reason: High conformational heterogeneity and structural variability prevented crystal formation
Molecular Details of Amyloid Formation by the Glaucoma-Associated Myocilin Olfactomedin (OLF) Domain · Georgia Tech · PhD
Tried and failed
crystal optimization and microseed matrix screening applied to recombinant bacterial protein crystallization. Outcome: no signal. Reason: failed to yield single, well-diffracting crystals suitable for X-ray diffraction
Structure/function analysis of a complex of minor pilins in the Streptococcus sanguinis Type IV Pili, mediating binding to host glycans · Imperial · Doctorate
Tried and failed
X-ray crystallization of multi-protein complex applied to heteropentameric protein kinase complex. Outcome: no signal. Reason: Extensive crystallization screening failed to produce diffraction-quality crystals of the co-complex.
Structural and functional studies of the AMP-activated protein kinase γ2 isoform · Imperial · PhD
Considered and rejected
Considered and rejected: X-ray crystallography of hSERINC5 was abandoned due to low solubility and hydrophobicity, pivoting to Cryo-EM with orthologs and Fab complexes.
Antiviral activity and retroviral counteraction of SERINC genes · University of Trento · PhD
Considered and rejected
Considered and rejected: X-ray crystallography of 16 truncated APOLLO fragments was rejected after failing to induce most fragments and recognizing intrinsic disorder precludes accurate reconstituted structure determination
Structural analysis of APOLLO, a candidate apomixis factor · Saskatchewan · Master's
Considered and rejected
Considered and rejected: X-ray crystallography of CD163 SRCR1-5 construct was abandoned after cryo-EM revealed heterogeneous oligomerisation (dimers/trimers) and domain flexibility
Structural basis of haptoglobin-haemoglobin scavenging by CD163 · Oxford · PhD
Considered and rejected
Considered and rejected: Rejected co-crystallizing 17β-HSD14 at cold room conditions (~4°C) due to failure to form crystals.
Mutational Studies on 17β-HSD14, Serial Synchrotron X-ray Crystallography, Solubility Enhancement using Cyclodextrins and Fragment-Based Drug Discovery Multiple Blocks to Pave the Road of Drug Design · University of Marburg · PhD
Considered and rejected
Considered and rejected: CRD-Fc fusion construct for X-ray crystallography (abandoned due to oligomeric heterogeneity and aberrant disulfide crosslinking).
Functional assessment of the cell entry pathway of Lymphocytic choriomeningitis virus · Harvard · PhD
Peak overlap and preferred orientation cause refinement instability and model mismatches
Powder and single-crystal Rietveld refinements failed to converge or match experimental profiles when high peak overlap and low-temperature peak asymmetry were present. Refinements were also hindered by non-random grain orientations, sheet-like morphologies, and unstable modeling of simultaneous positional and chemical disorder.
Tried and failed
single-crystal X-ray diffraction structure refinement applied to organic cocrystal hydrates. Outcome: did not converge. Reason: poor crystal diffraction quality prevented low R-factor refinement of all atoms
Crystallisation studies of glycine-based dipeptides: sequence-dependent solubility, cocrystal formation, and kinetics · Imperial · PhD
Tried and failed
Rietveld refinement of powder diffraction data applied to gas-loaded porous framework at low temperature. Outcome: did not converge. Reason: substantial peak asymmetry in low-temperature powder X-ray diffraction patterns
Tried and failed
stochastic stacking fault modelling applied to powder X-ray diffraction diffuse scattering. Reason: low-order layer history models could not reproduce specific asymmetric peak tails and diffuse features
Structural and thermodynamic studies of mixed metal halides for ammonia absorption applications · Oxford · PhD
Considered and rejected
Considered and rejected: Rejected single-crystal XRD refinement modeling of both positional and chemical disorder simultaneously in M-TCPB tetramers due to space group constraints and refinement instability
Computational Modeling of Energetic and Diffusion Properties in Metal-Organic Frameworks · Georgia Tech · PhD
Tried and failed
Rietveld refinement of X-ray diffraction patterns applied to quantifying structurally similar intermetallic phases. Outcome: no signal. Reason: diffraction peaks of the two candidate phases overlapped significantly
Process-microstructure-property relationships of high-pressure die cast AE44 magnesium alloy · Imperial · PhD
Tried and failed
Rietveld refinement of diffraction patterns applied to multiphase crystal structures. Outcome: did not converge. Reason: large number of phases and high degree of peak overlap prevented successful refinement
Design of Superelastic Secondary-Phase-Toughened Alloys · MIT · PhD
Tried and failed
direct powder-to-sintered pellet XRD pattern matching applied to sintered polycrystalline ceramic pellets. Outcome: did not generalise. Reason: preferential grain orientation and inhomogeneous phase distribution altered diffraction peak intensities
The Na|NaSICON interface in sodium solid-state batteries · Imperial · PhD
Considered and rejected
Considered and rejected: Rietveld XRD refinement rejected because heterogeneous serpentine ore forms sheet/cylinder structures violating random crystal orientation assumptions
Predicting Atmospheric CO2 Sequestration in Ultramafic Mine Tailings using an Empirically-Derived Model · Queen's University · Master's
Small-molecule and inorganic syntheses yield poor quality or mechanically fragile single crystals
Crystallization trials for coordination complexes, organic monomers, and salts frequently yielded only polycrystalline material or crystals of insufficient quality for single-crystal diffraction. Furthermore, formed crystals suffered from severe brittleness that led to breakage upon handling, or exhibited crystal twinning and background scattering that obscured light atom positions.
Tried and failed
Single-crystal growth for X-ray diffraction applied to functionalized conjugated organic monomers. Reason: Crystals produced were of insufficient quality for single-crystal X-ray diffraction analysis
Computational modelling of the effect of side chain chemistry on the micro-structure and electrolyte interactions of mixed transport polymers · Imperial · PhD
Considered and rejected
Considered and rejected: Rejected direct single-crystal X-ray diffraction for structure solution because large, high-quality single crystals could not be grown for metastable borides.
Unconventional synthesis of novel borides: interplay between crystal structures, magnetic and catalytic properties · Iowa State · PhD
Tried and failed
single-crystal X-ray diffraction applied to fragile organic molecular crystals. Outcome: unstable. Reason: Crystals were exceptionally brittle and bent or broke upon the slightest manipulation
Functional supramolecular architectures : mechanistic analysis of solid-state colorimetric switching and creation of novel energy conversion materials · UT Austin · PhD
Tried and failed
single-crystal growth for X-ray diffraction applied to doubly oxidized iron-sulfur cluster complex. Reason: crystals of sufficient quality for X-ray diffraction could not be obtained
Investigations of Iron–Nitrogen Bonding at Synthetic Iron–Sulfur Clusters · MIT · PhD
Tried and failed
Single-crystal X-ray diffraction structure determination applied to heavy metal carboxylate coordination complexes. Reason: Crystal twinning and high background scattering prevented resolving light hydrogen atom positions
Natural deep eutectic solvents (NADESs) for lead acid battery recycling · Imperial · PhD
Tried and failed
single-crystal growth for X-ray diffraction applied to polyquaternary ammonium salt derivatives. Reason: Failed to form diffraction-quality single crystals despite multiple conditions
Total Synthesis of Oligomeric Cyclotryptamine Alkaloids · MIT · PhD
Tried and failed
Single crystal growth for X-ray diffraction applied to copper coordination complex. Reason: Crystallization attempts yielded only polycrystalline material instead of single crystals
Chemical Sensing of N-Nitrosodimethylamine and Methane · MIT · PhD
X-ray beam damage and low scattering contrast constrain diffraction measurements
Structural determinations were obstructed when heavy elements dominated scattering over light elements or when samples exhibited excessive X-ray absorption. Experimental accuracy was also compromised by beam-induced lattice parameter shifts, non-linear diffraction decay, and insufficient diffraction peaks for microstrain analysis.
Tried and failed
generative structure prediction from powder diffraction patterns applied to crystals containing light elements. Outcome: no signal. Reason: Weak X-ray scattering of low-Z elements yields insufficient diffraction signal to resolve complex bonding structures.
Order Under Pressure: Structural and Magnetic Characterization at Extreme Stresses · MIT · PhD
Considered and rejected
Considered and rejected: Rejected using fully amorphous diffraction patterns as the end point for critical dose calculations to avoid overestimating crystal radiation tolerance, opting instead for the penultimate pre-fading pattern
Chemical transformations in the transmission electron microscope · Nottingham · PhD
Considered and rejected
Considered and rejected: Rejected relying on single-crystal XRD alone for structural validation of LiNiB and ternary phosphides because heavy transition metals (Ni, Ru, Ir) dominate scattering over light elements (Li, B, Si, P).
Improving sensitivity and resolution in solid-state nuclear magnetic resonance · Iowa State · PhD
Considered and rejected
Considered and rejected: Rejected X-ray diffraction (XRD) on whole fibers because it requires quarter-sized samples incompatible with minimally destructive archaeological analysis
The Paisley Caves: A Paleoethnobotanical Approach to Textiles Studies in the Northern Great Basin, Oregon · University of Oregon · PhD
Tried and failed
inelastic x-ray scattering phonon dispersion measurement applied to organic and hybrid crystal acoustic phonons. Outcome: unstable. Reason: X-ray beam damage caused a 0.5% lattice parameter shift during measurement
EXPLORING THERMAL TRANSPORT IN ORGANIC AND HYBRID MATERIALS · Cornell · PhD
Tried and failed
uncalibrated X-ray diffraction applied to measuring polymer crystallinity. Outcome: worse than baseline. Reason: produced mismatched crystallinity values compared to calorimetry due to lack of a known standard calibration
Tried and failed
linear resolution dependent decay modeling applied to macromolecular X-ray diffraction intensity decay. Outcome: did not generalise. Reason: linear exponent fails to match non-linear experimental diffraction decay profiles across datasets
Considered and rejected
Considered and rejected: Rejected Williamson-Hall analysis on XRD profiles because PCL did not possess a sufficient number of diffraction peaks to yield an accurate deconvolution of crystal size and microstrain.
Microstructural evolution of electrospun microfibers for biomedical applications · Oxford · Master's
Powder diffraction lacks sensitivity to identify amorphous or nanoscale phases
Powder X-ray diffraction failed to resolve or differentiate target phases when materials were amorphous, nanoscale, or present at concentrations below detection limits. Peak broadening from decompression or matrix overlap also prevented assigning specific crystalline phases in complex residues and metallic alloys.
Tried and failed
powder X-ray diffraction phase identification applied to surface-deposited metal oxide coatings on carbon. Outcome: no signal. Reason: Deposited oxides were amorphous, nanoscale, and present at low surface concentrations below detection thresholds.
Treatment of Aqueous Arsenic Using Chemically and Electrochemically Modified Biomaterials · Saskatchewan · PhD
Tried and failed
laboratory X-ray diffraction phase characterization applied to nanoscale secondary precipitates in metallic alloys. Outcome: no signal. Reason: Instrument resolution and signal overlap failed to resolve and differentiate nanoscale phase peaks from matrix phases
Microstructural Prediction of Additively Manufactured Multi-Phase Materials · Georgia Tech · PhD
Tried and failed
standard powder X-ray diffraction applied to micrometer-scale mineral structures. Reason: structures were too small (1 to 6 µm) to sample or analyze via standard powder XRD
Chemistry of the pearl oyster Pinctada radiata and implications for palaeoceanography · Queen's University · Doctorate
Tried and failed
powder X-ray diffraction phase identification applied to amorphous chemical precipitation wastewater residuals. Outcome: no signal. Reason: residuals lacked crystalline phases and failed to match standard database reference patterns
Evaluation of plant-available phosphorus of residuals from wastewater processed for phosphorus reduction · Iowa State · Master's
Tried and failed
powder X-ray diffraction phase identification applied to biomass-derived complex multiphase chars. Reason: complex sharp diffraction peaks prevented assignment of specific crystalline inorganic phases
Understanding the relationship between synthetic conditions, porosity and CO2 uptake capacity of turbostratic carbons · Nottingham · PhD
Tried and failed
in situ high-temperature x-ray diffraction applied to short-range order-disorder phase transitions in alloys. Outcome: no signal. Reason: XRD lacked sensitivity to detect short-range ordering (k-state) causing calorimetric specific heat anomalies
Thermophysical and Molten Salt Corrosion Behavior of Structural Materials for Next-Generation Clean Energy Systems · Georgia Tech · PhD
Tried and failed
powder x-ray diffraction phase identification after decompression applied to quenched high-pressure metastable intermetallic mixtures. Outcome: no signal. Reason: decompression caused broad diffraction peaks that prevented uniquely distinguishing and assigning recovered phases
Emergent Properties in Intermetallic Bismuth Binaries · MIT · PhD
Left open by the authors
Problems the authors named and did not get to.
Left open
Crystallize and solve the X-ray crystal structure of the dimeric extracellular domain of mincle. Blocker: Requires wet-lab protein purification, crystallization trials, and X-ray diffraction facilities
Importance of receptor geometry for initiation of signalling by the mincle family of glycan-binding receptors · Imperial · PhD
Left open
Structurally characterize intact BsuMI and LlaI R1-R2 or R1:R2:R3 protein complexes using X-ray crystallography or cryo-EM. Blocker: Requires a wet lab, protein expression/purification, and access to X-ray crystallography or cryo-EM facilities.
INVESTIGATING THE EVOLUTION OF NUCLEOTIDE SPECIFICITY AND ORGANIZATION OF DNA BINDING IN MCRBC COMPLEXES · Cornell · PhD
Left open
Solve the ternary complex structure of CRBN/FPFT-2216/PPIL4 using cryo-EM or X-ray crystallography. Blocker: Requires wet lab facilities, protein expression/purification, and cryo-EM or X-ray crystallography equipment.
Mass Spectrometry-Based Proteomics Approaches to Define Enzyme-Substrate Relationships in the Ubiquitin Proteasome System · Harvard · PhD
Left open
Resolve WCC-C-box crystal structures using the identified minimal DNA binding sequences or cryo-EM. Blocker: Requires wet lab facilities, protein/DNA sample preparation, and X-ray crystallography or cryo-EM equipment.
THE NEUROSPORA CRASSA CIRCADIAN CLOCK: AN ORDERLY LOOP DRIVEN BY A DISORDERED CONDUCTOR · Cornell · PhD
Left open
Determine the membrane binding mechanisms and oligomerization states of BcLOV4 using cryo-electron microscopy or X-ray crystallography. Blocker: Requires a wet lab, protein purification, and structural biology experimental apparatus (cryo-EM/X-ray crystallography)
Biophysical Dynamics Of Rgs-Lov Proteins As Systems For Light-Induced Membrane Recruitment · Penn · PhD
Left open
Determine the structure of the Zpr1-eEF1A-Aim29-GTP-γ-S quaternary complex using cryo-EM or X-ray crystallography. Blocker: Requires a structural biology wet lab with access to cryo-EM or crystallography facilities and protein expression/purification
The tailored chaperone pathway for eukaryotic elongation factor 1A (eEF1A) biogenesis · Harvard · PhD
Left open
Determine high-resolution cryo-EM or X-ray crystal structures of cytotoxic TG2 forms, including the R580K open state dimer and inhibitor complexes. Blocker: Requires wet-lab protein expression, purification, crystallization/cryo-EM grid preparation, and access to X-ray beamlines or cryo-EM facilities
BIOCHEMICAL AND STRUCTURAL CHARACTERIZATION OF G PROTEIN-COUPLED RECEPTOR ASSOCIATED ENZYMES · Cornell · PhD
Left open
Perform structural characterisation of UapA-WT or UapA-Q408EΔ1-11 bound to 3-benzylxanthine using cryo-EM and X-ray crystallography. Blocker: Requires wet lab facilities, purified protein samples, chemical analogues, and cryo-EM/crystallography equipment
Structural and functional characterisation of Uric Acid Permease, a fungal nucleobase transporter, with novel substrates · Imperial · PhD
Left open
Resolve the crystal structure of MAB_2736c bound to the mycobacterial ribosome using X-ray crystallography or cryo-EM. Blocker: Requires wet lab facilities for protein/ribosome purification and X-ray crystallography or cryo-EM structural determination
Genetic determinants of antibiotic susceptibility reveal novel mechanisms of action and resistance in mycobacteria · Harvard · PhD
Who has worked on this
Authors of the public theses cited on this page, most-cited first.
- Anthony Bui · Cornell · PhD · 2024
INVESTIGATING THE EVOLUTION OF NUCLEOTIDE SPECIFICITY AND ORGANIZATION OF DNA BINDING IN MCRBC COMPLEXES - Samuel Alexander Carlson · Harvard · PhD · 2023
Structural Understanding of Remodeling Function of HIV-1 Reverse Transcriptase During Initiation - Kim Walbrunn · Leibniz Universität Hannover · PhD · 2026
Structural determination of Entamoeba Histolytica TGT and its binding to tRNAASP - Sorin Asha Srinivasa · MIT · PhD · 2025
Structural and biochemical investigations of collagen-I trimerization - Olivia Zhang · Harvard · PhD · 2025
Elucidating novel chemical and genetic mechanisms of LSD1-HDAC1/2-CoREST complex regulation - Alan Wylde Carter · MIT · PhD · 2025
Structural Insights into Mycobacteriales Galactan Biosynthesis - Eric Alan Riesel · MIT · PhD · 2025
Order Under Pressure: Structural and Magnetic Characterization at Extreme Stresses - Catherine Kyoko Badding · MIT · PhD · 2025
Emergent Properties in Intermetallic Bismuth Binaries - Haosheng Feng · MIT · PhD · 2025
Chemical Sensing of N-Nitrosodimethylamine and Methane - Enshu Liang · Imperial · PhD · 2024
Crystallisation studies of glycine-based dipeptides: sequence-dependent solubility, cocrystal formation, and kinetics - Kerry Alexandra McGowen · Harvard · PhD · 2024
Genetic determinants of antibiotic susceptibility reveal novel mechanisms of action and resistance in mycobacteria - Dvir Reif · Harvard · PhD · 2024
The tailored chaperone pathway for eukaryotic elongation factor 1A (eEF1A) biogenesis
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