About

Professor Thomas Cheatham leads a research group focused on the use and development of molecular dynamics, free energy simulation, and trajectory analysis methodologies, with a particular emphasis on the AMBER software suite. His research aims to enhance the understanding of biomolecular structure, dynamics, and interactions, concentrating on the accurate modeling of nucleic acids and proteins and their responses to ligands or environmental changes. The group is recognized for identifying and addressing problems with force fields and computational methods, dedicating significant effort to improving these tools and facilitating research in the field. In addition to his research activities, Professor Cheatham has held leadership roles in research computing at the University of Utah, including serving as the Director of Research Computing and the Center for High Performance Computing (CHPC) within University Information Technology. He has also been actively involved with the Campus Research Computing Consortium (CaRCC), serving as Interim Council Chair, Council Chair, and currently as Acting Chair. His professional activities reflect a commitment to advancing computational resources and infrastructure to support scientific research.

Research topics

• Computer Science
• Information Retrieval
• Database
• Biology
• Knowledge management
• Software engineering
• Data science
• Engineering management
• Chemistry
• Genetics
• Computational chemistry
• Engineering
• Biophysics
• World Wide Web
• Programming language
• Management

Selected publications

• Author response for "Blind Prediction of Complex Water and Ion Ensembles Around <scp>RNA</scp> in <scp>CASP16</scp>"

  2025-10-06

  peer-review
  PublisherDOI

• Correction to “Molecular Modeling of Single- and Double-Hydrocarbon-Stapled Coiled-Coil Inhibitors against Bcr-Abl: Toward a Treatment Strategy for CML”

  The Journal of Physical Chemistry B · 2025-07-03

  erratumOpen accessSenior author
  PublisherDOI

• Application of Computed FTIR Spectra of Nucleotide Monophosphates to RNA Force Field Refinement

  Journal of Chemical Theory and Computation · 2025-08-08 · 1 citations

  articleSenior authorCorresponding

  We use the Hessian Matrix reconstruction (HMR) method to compute Fourier transform infrared (FTIR) spectra in the amide I region of nucleotide monophosphates solvated in TIP3P water and in OPC water from molecular dynamics simulations with the Amber OL3/OL15 force fields, and compare these to experimental spectra. The spectrum of TMP in TIP3P water fails to correctly capture the relative amplitudes of peaks in the amide I region when compared to experiment. Moreover, despite improvement in RNA conformations previously reported when using the OPC water model compared to TIP3P, the spectra of CMP and UMP solvated by OPC water model showed little resemblance to experimental spectra. Current van der Waals (vdW) parameters for RNA in the popular AMBER OL3/OL15 force fields were developed to reproduce neat liquid properties, while neglecting long-range electrostatic interactions, and have not undergone updates for several decades. Therefore, we varied the vdW radii of nucleic acid base amide O atoms to try to improve the FTIR spectra of TMP, CMP and UMP in OPC water. For all three pyrimidine monophosphates, we observed significant improvements in computed RNA spectra when the vdW radii of amide O were increased by 7.5%. We also confirmed that this change resulted in improved densities and enthalpies of solvation of three different solvents containing amide groups, as well as in improved simulated conformational equilibria of the r(CCCC) tetranucleotide. This result warrants future testing of the effect of our proposed force field modification on the accuracy of prediction of RNA conformational equilibria by molecular dynamics simulations employing the Amber OL3 force field.

  PublisherDOI

• Blind Prediction of Complex Water and Ion Ensembles Around <scp>RNA</scp> in <scp>CASP16</scp>

  Proteins Structure Function and Bioinformatics · 2025-11-08 · 1 citations

  articleOpen access

  Biomolecules rely on water and ions for stable folding, but these interactions are often transient, dynamic, or disordered and thus hidden from experiments and evaluation challenges that represent biomolecules as single, ordered structures. Here, we compare blindly predicted ensembles of water and ion structure to the cryo-EM densities observed around the Tetrahymena ribozyme at 2.2-2.3 Å resolution, collected through target R1260 in the CASP16 competition. Twenty-six groups participated in this solvation "cryo-ensemble" prediction challenge, submitting over 350 million atoms in total, offering the first opportunity to compare blind predictions of dynamic solvent shell ensembles to cryo-EM density. Predicted atomic ensembles were converted to density through local alignment and these densities were compared to the cryo-EM densities using Pearson correlation, Spearman correlation, mutual information, and precision-recall curves. These predictions show that an ensemble representation is able to capture information of transient or dynamic water and ions better than traditional atomic models, but there remains a large accuracy gap to the performance ceiling set by experimental uncertainty. Overall, molecular dynamics approaches best matched the cryo-EM density, with blind predictions from bussilab_plain_md, SoutheRNA, bussilab_replex, coogs2, and coogs3 outperforming the baseline molecular dynamics prediction. This study indicates that simulations of water and ions can be quantitatively evaluated with cryo-EM maps. We propose that further community-wide blind challenges can drive and evaluate progress in modeling water, ions, and other previously hidden components of biomolecular systems.

  PublisherOA PDFDOI

• Blind prediction of complex water and ion ensembles around RNA in CASP16

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-11-03

  preprintOpen access

  Abstract Biomolecules rely on water and ions for stable folding, but these interactions are often transient, dynamic, or disordered and thus hidden from experiments and evaluation challenges that represent biomolecules as single, ordered structures. Here, we compare blindly predicted ensembles of water and ion structure to the cryo-EM densities observed around the Tetrahymena ribozyme at 2.2-2.3 Å resolution, collected through target R1260 in the CASP16 competition. 26 groups participated in this solvation ‘cryo-ensemble’ prediction challenge, submitting over 350 million atoms in total, offering the first opportunity to compare blind predictions of dynamic solvent shell ensembles to cryo-EM density. Predicted atomic ensembles were converted to density through local alignment and these densities were compared to the cryo-EM densities using Pearson correlation, Spearman correlation, mutual information, and precision-recall curves. These predictions show that an ensemble representation is able to capture information of transient or dynamic water and ions better than traditional atomic models, but there remains a large accuracy gap to the performance ceiling set by experimental uncertainty. Overall, molecular dynamics approaches best matched the cryo-EM density, with blind predictions from bussilab_plain_md, SoutheRNA, bussilab_replex, coogs2, and coogs3 outperforming the baseline molecular dynamics prediction. This study indicates that simulations of water and ions can be quantitatively evaluated with cryo-EM maps. We propose that further community-wide blind challenges can drive and evaluate progress in modeling water, ions and other previously hidden components of biomolecular systems.

  PublisherOA PDFDOI

• Parameterizing modified nucleic acids for molecular simulations in the AMBER MD software environment [Article v1.0]

  Living Journal of Computational Molecular Science · 2025-12-31

  articleOpen access

  Parameterizing modified nucleic acids is a difficult but necessary task for expanding the simulated space of oligonucleotides, including both naturally occurring structures and those with pharmaceutical relevance. In lieu of expensive and difficult chemical synthesis in the laboratory, computer simulations are often performed to make predictions for sequence and structure effects, as well as downstream critical quality attributes. To enable these simulations, modifications have to be parameterized to faithfully represent their effect on nucleotides. This is a non-trivial process, complicated by the fact that it may be the first thing researchers must figure out before they can build their structures and start their initial simulations. To enable these research projects, we created modXNA, a code that assembles pre-parameterized modules of the base, backbone, and sugar, to create bespoke combinations of modifications. In the following tutorial, we provide background on force field parameterization in the Amber software ecosystem and detail the steps necessary to perform parameterization of modified nucleic acids using modXNA.

  PublisherDOI

• The need to implement FAIR principles in biomolecular simulations

  Nature Methods · 2025-04-01 · 53 citations

  articleOpen access
  PublisherOA PDFDOI

• Recent Developments in Amber Biomolecular Simulations

  Journal of Chemical Information and Modeling · 2025-07-29 · 81 citations

  articleOpen access

  module is available as a serial version for central processing units (CPUs), NVIDIA and Advanced Micro Devices (AMD) graphics processing unit (GPU) versions as well as Message Passing Interface (MPI) parallel versions. Advanced capabilities include thermodynamic integration, replica exchange MD and accelerated MD methods. A brief update to the software and recently added capabilities is described in this Application Note.

  PublisherDOI

• The mechanism of covalent inhibition of LAR phosphatase by illudalic acid

  Bioorganic & Medicinal Chemistry Letters · 2024-04-09 · 1 citations

  articleOpen access
  PublisherOA PDFDOI

• Molecular Modeling of Single- and Double-Hydrocarbon-Stapled Coiled-Coil Inhibitors against Bcr-Abl: Toward a Treatment Strategy for CML

  The Journal of Physical Chemistry B · 2024-07-01 · 3 citations

  articleOpen accessSenior authorCorresponding

  The chimeric oncoprotein Bcr-Abl is the causative agent of virtually all chronic myeloid leukemias and a subset of acute lymphoblastic leukemias. As a result of the so-called Philadelphia chromosome translocation t(9;22), Bcr-Abl manifests as a constitutively active tyrosine kinase, which promotes leukemogenesis by activation of cell cycle signaling pathways. Constitutive and oncogenic activation is mediated by an N-terminal coiled-coil oligomerization domain in Bcr (Bcr-CC), presenting a therapeutic target for inhibition of Bcr-Abl activity toward the treatment of Bcr-Abl+ leukemias. Previously, we demonstrated that a rationally designed Bcr-CC mutant, CCmut3, exerts a dominant negative effect upon Bcr-Abl activity by preferential oligomerization with Bcr-CC. Moreover, we have shown that conjugation to a leukemia-specific cell-penetrating peptide (CPP-CCmut3) improves intracellular delivery and activity. However, our full-length CPP-CCmut3 construct (81 aa) is encumbered by an intrinsically high degree of conformational variability and susceptibility to proteolytic degradation relative to traditional small-molecule therapeutics. Here, we iterate a new generation of CCmut3 inhibitors against Bcr-CC-mediated Bcr-Abl assembly designed to address these constraints through incorporation of all-hydrocarbon staples spanning i and i + 7 positions in α-helix 2 (CPP-CCmut3-st). We utilize computational modeling and biomolecular simulation to evaluate single- and double-stapled CCmut3 candidates in silico for dynamics and binding energetics. We further model a truncated system characterized by the deletion of α-helix 1 and the flexible loop linker, which are known to impart high conformational variability. To study the impact of the N-terminal cyclic CPP toward model stability and inhibitor activity, we also model the full-length and truncated systems devoid of the CPP, with a cyclized CPP, and with an open-configuration CPP, for a total of six systems that comprise our library. From this library, we present lead-stapled peptide candidates to be synthesized and evaluated experimentally as our next iteration of inhibitors against Bcr-Abl.

  PublisherOA PDFDOI

Recent grants

• NIH Grant P41RR001081

  NIH · $4.6M · 2012

• PRAC - Hierarchical molecular dynamics sampling for assessing pathways and free energies of RNA catalysis, ligand binding, and conformational change

  NSF · $40k · 2011–2015

• NIH Grant R01GM098102

  NIH · $2.1M · 2016

• CDS&E: Tools to facilitate deeper data analysis, exploration, management, and sharing of ensembles of molecular dynamics trajectory data

  NSF · $300k · 2013–2016

• PRAC - Ensembles of Molecular Dynamics Engines for Assessing Force Fields, Conformational Change, and Free Energies of Proteins and Nucleic Acids

  NSF · $40k · 2015–2019

Frequent coauthors

• Jiřı́ Šponer

  Czech Academy of Sciences, Institute of Biophysics

  193 shared

• Modesto Orozco

  Universitat de Barcelona

  105 shared

• David A. Case

  Rutgers, The State University of New Jersey

  104 shared

• Nad’a Špačková

  Masaryk University

  92 shared

• Filip Lankaš

  University of Chemistry and Technology, Prague

  72 shared

• Rodrigo Galindo‐Murillo

  Ionis Pharmaceuticals (United States)

  71 shared

• Alberto Pérez

  University of Florida

  57 shared

• Peter A. Kollman

  Rutgers, The State University of New Jersey

  52 shared

Education

• B.A.

  Middlebury College

• Ph.D.

  University of California, San Francisco