Software

Our research generates and refines open-source and proprietary software tools that are central to the field of computational molecular science. These tools are often available for academic and industry use.

Software from the Guidez Group

Emilie Guidez

Professor Guidez is a developer for the QMMM and GAMESS software packages. For more information about her software contact her at EMILIE.GUIDEZ@UCDENVER.EDU.

Name: IAP (Interpolated Adaptive Partitioning) / APML (Adaptive Partitioning Multilayer)
Description: An alchemical method to smooth Q1-Q2 transitions in three-layer QM/QM/MM
Publication and Update:
Mato, J.; Duster, A. W.; Guidez, E. B.; Lin, H. J. Chem. Theory Comput. 2021, 17, 5456-5465
Tran, A. L.; Guidez, E. B.; Lin, H. J. Phys. Chem. A 2023, 127, 10320-10333

Software from the Lee Group

Woonghee Lee

For more information about POKY and other software, contact him at WOONGHEE.LEE@UCDENVER.EDU

Name: POKY 
Description: Comprehensive, AI-integrated software suite for multidimensional NMR data analysis, automated resonance assignment, 3D structure calculation, dynamics, metabolomics, and computer-aided drug design. 
Publication: Lee W, Rahimi M, Lee Y, Chiu A. Bioinformatics 2021, 37(18):3041-3042. https://doi.org/10.1093/bioinformatics/btab180 (See also: Chiu A, Lee W. Journal of Biological Chemistry 2026, 302(3):111246.)

Name: POKY Structure Builder 
Description: One-click interface in POKY for setting up PONDEROSA-based NMR-restrained 3D structure calculation from the active project — inputs protein sequence, chemical shift assignments, and NOESY peak lists. 
Publication: Lee W, Rahimi M, Lee Y, Chiu A. Bioinformatics 2021, 37(18):3041-3042. https://doi.org/10.1093/bioinformatics/btab180

Name: POKY Structure Analyzer 
Description: POKY's structure validation and visualization module — inspects PONDEROSA outputs with PyMOL, RMSD tables, Ramachandran analysis, and restraint violation reports. 
Publication: Lee W, Rahimi M, Lee Y, Chiu A. Bioinformatics 2021, 37(18):3041-3042. https://doi.org/10.1093/bioinformatics/btab180

Name: CHESPA / CHESCA-SPARKY 
Description: Automated NMR data analysis tools for mapping protein allostery — CHESCA (Chemical Shift Covariance Analysis) identifies allosteric networks from correlated chemical shift changes; CHESPA (Chemical Shift Projection Analysis) maps directional allostery. Integrated as a POKY extension. 
Publication: Lee W et al. Bioinformatics 2021, 37(8):1176-1177. https://doi.org/10.1093/bioinformatics/btaa781

Name: Versatile Assigner 
Description: Semi-automated NMR assignment tool in POKY. Extending assignment-guessing across multiple spectra and constraint types after backbone completion. 
Publication: Manthey I, Tonelli M, Clos L 2nd, Rahimi M, Markley JL, Lee W. Journal of Structural Biology: X 2022, 6:100073. https://doi.org/10.1016/j.yjsbx.2022.100073

Name: iPick 
Description: Versatile automated peak picker in POKY for diverse spectrum types beyond backbone-focused APES, with integration for REDEN multi-component decomposition in crowded regions. 
Publication: Manthey I, Tonelli M, Clos L 2nd, Rahimi M, Markley JL, Lee W. Journal of Structural Biology: X 2022, 6:100073. https://doi.org/10.1016/j.yjsbx.2022.100073

Name: pyLACS 
Description: Linear Analysis of Chemical Shifts — identifies chemical shift assignment outliers and corrects referencing errors in protein NMR data. 
Publication: Manthey I, Tonelli M, Clos L 2nd, Rahimi M, Markley JL, Lee W. Journal of Structural Biology: X 2022, 6:100073. https://doi.org/10.1016/j.yjsbx.2022.100073

Name: AUDASA 
Description: Automated unified NOE crosspeak assignment using the PACSY chemical shift database and ESMFold structure predictions to generate distance constraints for 3D structure calculation. 
Publication: Rahimi M, Lee Y, Nguyen H, Chiu A, Lee W. Journal of Magnetic Resonance 2022, 339:107214. https://doi.org/10.1016/j.jmr.2022.107214

Name: ssPINE 
Description: Probabilistic algorithm for automated chemical shift assignment of solid-state NMR data from complex protein systems, including membrane proteins. 
Publication: Dwarasala A, Rahimi M, Markley JL, Lee W. Membranes 2022, 12(9):834. https://doi.org/10.3390/membranes12090834

Name: TINTO 
Description: Computer vision-based NMR walking strategy embedded in POKY for rapid backbone resonance tracking and strip-plot navigation. 
Publication: Lopez Giraldo AE, Werner Z, Rahimi M, Lee W. Journal of Biomolecular NMR 2023, 77(5-6):217-228. https://doi.org/10.1007/s10858-023-00423-6

Name: REDEN 
Description: Interactive multi-fitting decomposition-based NMR peak picking assistant for crowded spectral regions, integrated with iPick in POKY. 
Publication: Rahimi M, Chiu A, Lopez Giraldo AE, Yoon JH, Lee W. Journal of Magnetic Resonance 2024, 358:107600. https://doi.org/10.1016/j.jmr.2023.107600

Name: A-SIMA / A-MAP 
Description: A-SIMA (Advanced Software for Interactive Metabolite Analysis) and A-MAP (A Multivariate Analysis Program, PCA/OPLS-DA) — a comprehensive toolkit for NMR-based metabolomics analysis from 1D and 2D NMR spectra. 
Publication: Chiu A, Rahimi M, Lee W. Metabolomics 2025, 21:10. https://doi.org/10.1007/s11306-024-02208-w

Name: ssPINE 
Description: Probabilistic algorithm for automated chemical shift assignment of solid-state NMR data from complex protein systems, including membrane proteins. 
Publication: Dwarasala A, Rahimi M, Markley JL, Lee W. Membranes 2022, 12(9):834. https://doi.org/10.3390/membranes12090834

Name: PISA-POKY 
Description: POKY reimplementation of PISA-SPARKY — exhaustive PISA-wheel fitting for oriented solid-state NMR spectra of helical membrane proteins, determining precise tilt and rotation angles of alpha-helical segments. Originally published as PISA-SPARKY; continuously updated at CU Denver as part of POKY. 
Publication: (Original) Weber DK, Wang S, Markley JL, Veglia G, Lee W. Bioinformatics 2020, 36(9):2915-2916. https://doi.org/10.1093/bioinformatics/btaa019

Name: Titration Plot / Perturbation Plot 
Description: Interactive tools for chemical shift perturbation analysis — Titration Plot (ni) fits binding curves and calculates Kd from shift changes across a ligand titration series; Perturbation Plot (np) maps binding events by comparing chemical shift changes before and after ligand addition. Originally introduced at NMRFAM; continuously updated at CU Denver as part of POKY. 
Publication: (Original) Lee W, Cornilescu G, Dashti H, Eghbalnia HR, Tonelli M, Westler WM, Butcher SE, Henzler-Wildman KA, Markley JL. Journal of Biomolecular NMR 2016, 64(4):307-332. https://doi.org/10.1007/s10858-016-0029-x

Name: I-PINE for POKY (Enhanced I-PINE) 
Description: Enhanced version of the I-PINE probabilistic NMR assignment engine built directly into POKY, surpassing the original I-PINE web server in accuracy and coverage. Supports 38 solution-state NMR experiments including 13C-detected and MOCCA-based experiments for intrinsically disordered proteins (M-PINE module). No independent paper yet — included in POKY. 
Publication: (Original I-PINE) Lee W, Bahrami A, Dashti HT, Eghbalnia HR, Tonelli M, Westler WM, Markley JL. Journal of Biomolecular NMR 2019, 73(5):213-222. https://doi.org/10.1007/s10858-019-00255-3

Software from the Lin Group

Hai Lin

For more information about Professor Lin’s software, contact him at HAI.LIN@UCDENVER.EDU 

QMMM is a collaborative effort between Donald G. Truhlar at the University of Minnesota Twin Cities, and Hai Lin at the University of Colorado Denver. The Minnesota version is called QMMM and the Colorado version is called QMMM 3.0.0.CO (for Colorado). Both versions are completely open source. Various software tools created by the Lin group are listed below.

Name: QMMM
First release: version 1.0.0 in 2005
Current release: version 2023 in 2022.
Description: QMMM is a computer program for performing single-point calculations (energies, gradients, and Hessians), geometry optimizations, and molecular dynamics using combined quantum-mechanics (QM) and molecular-mechanics (MM) methods. It calls a QM package and an MM package to perform the required single-level calculations and combines them into a QM/MM energy by a variety of schemes. It features a series of unique algorithms, such as the flexible-boundary scheme that allows partial charge transfer between QM and MM subsystems and the adaptive-partitioning scheme that permits exchange of particles between QM and MM subsystems on-the-fly during dynamics simulations.
Publication: Lin, H.; Zhang, Y.; Pezeshki, S.; Duster, A. W.; Wang, B.; Wu, X.-P.; Zheng, S.-W. Gagliardi, L.; Truhlar, D. G. "QMMM 2023: A program for combined quantum mechanical and molecular mechanical modeling and simulations," Comput. Phys. Commun. 2023, 295, 108987.
Link: https://comp.chem.umn.edu/qmmm/

Name: QMMM 3.0.0.CO
Link: https://clas.ucdenver.edu/hai-lin/ 
Overview Publications:
Lin, H.; Truhlar, D. G. “QM/MM: What have we learned, where are we, and where do we go from here?” Theor. Chem. Acc. 2007, 117, 185-199
Duster, A. W., Wang, C.-H., Garza, C. M., Miller, D. E. & Lin, H. “Adaptive quantum/molecular mechanics: What have we learned, where are we, and where do we go from here?” Wiley Interdiscip. Rev. Comput. Mol. Sci. 2017. 7, e1310
Lin, H. QM/MM Methods. In ACS In Focus, 2024, American Chemical Society

Name: RC (Redistributed Charge) / RCD (Redistributed Charge and Dipole)
Description: Schemes that handle link atoms in QM/MM
Publication: Lin, H.; Truhlar, D. G. J. Phys. Chem. A 2005, 109, 3991-4004

Name: PBRC (Polarized Boundary RC) and PBRCD (Polarized Boundary RCD)
Description: Self-consistent mutual polarization of the boundary region of the MM subsystem in QM/MM
Publication: Zhang, Y; Lin, H.; Truhlar, D. G.  J. Chem. Theory Comput. 2007, 3, 1378-1398 

Name: FBRC (Flexible Boundary RC) and FBRCD (Flexible Boundary RCD)
Description: A flexible-boundary scheme for partial charge transfers between the quantum-mechanical (QM) and molecular-mechanical (MM) subsystems in QM/MM 
Publication and Updates:
Zhang, Y; Lin, H.  J. Chem. Theory Comput. 2008, 4, 414-425 
Zhang, Y; Lin, H. Theor. Chem. Acc. 2010, 216, 315-322 
Pezeshki, S.; Lin, H. J. Comput. Chem. 2014, 35, 1778-1788 

Name: APRC (Adaptive Partitioning RC) and APRCD (Adaptive Partitioning RCD)
Description: On-the-fly relocation of boundaries that pass through covalent bonds for the RC and RCD schemes in QM/MM
Publication and Update:
Heyden, A.; Lin, H.; Truhlar, D. G.  J. Phys. Chem. B. 2007, 111, 2231-2241 
Pezeshki, S.; Lin, H.  J. Chem. Theory Comput. 2011, 7, 3625-3634

Name: Modified PAP (Permuted Adaptive Partitioning)
Description: A modified PAP scheme of QM/MM for the exchange of solvent molecules between a protein binding site and bulk solvent
Publication: Pezeshki, S.; Davis, C.; Heyden, A.; Lin, H. J. Chem. Theory Comput. 2014, 10, 4765-4776

Name: Proton Indicator
Description: A tool for studying proton transfer in solution using the modified permuted adaptive-partitioning scheme
Publication and Updates: 
Pezeshki, S.; Lin, H. J. Chem. Theory Comput. 2015, 11, 2398-2411 
Duster, A.; Lin, H. J. Phys. Chem. B 2017, 121, 8585-8592
Duster, A. W.; Lin, H. J. Chem. Theory Comput. 2019, 15, 5794-5809
Talachutla, S.; Bhat, S.; Duster, A. W.; Lin, H. Chem. Phys. Lett. 2021, 784, 139121
Yan, S.; Wang, B.; Lin, H. J. Chem. Theory Comput. 2023, 19, 448-459
Yan, S.; Wang, B.; Lin, H. J. Chem. Theory Comput. 2024, 20, 3462-3472

Name: HPAP (HAMBC-PAP)
Description: A tailored version of the Hamiltonian adaptive many-body correction (HAMBC) to the permuted AP (PAP) scheme
Publication: Duster, A., Wang, C-H., Lin, H. Molecules, 2018, 121, 8585-8592

Name: IAP (Interpolated Adaptive Partitioning) / APML (Adaptive Partitioning Multilayer)
Description: An alchemical method to smooth Q1-Q2 transitions in three-layer QM/QM/MM
Publication and Update:
Mato, J.; Duster, A. W.; Guidez, E. B.; Lin, H. J. Chem. Theory Comput. 2021, 17, 5456-5465
Tran, A. L.; Guidez, E. B.; Lin, H. J. Phys. Chem. A 2023, 127, 10320-10333 

Name: Adaptive-Shape QM/MM
Description: A new way to set up the QM zone in QM/MM, where only the water molecules important to proton transfer are included
Publication: Yan, S.; Wang, B.; Lin, H. J. Chem. Theory Comput. 2024, 20, 3462-3472

Software from the Pourkamali Group

Farhad Pourkamali

For more information about Professor Pourkamali’s software, contact him at FARHAD.POURKAMALI@UCDENVER.EDU

Name: AleaQuant: Adaptive Aleatoric Uncertainty Estimation
Description: AleaQuant is a software framework for adaptive probabilistic modeling that estimates aleatoric uncertainty, enabling prediction uncertainty to vary across individual observations instead of assuming constant noise. The software supports flexible probability distributions beyond Gaussian assumptions, providing reliable uncertainty estimates for heterogeneous data across scientific and engineering applications.
Publication: Pourkamali-Anaraki, F. (2026). Probabilistic Neural Networks (PNNs) with t-distributed outputs: adaptive prediction intervals beyond Gaussian assumptions. Neural Computing and Applications, 38(8), 259.

Name: SelectAI: Selective Prediction for Reliable AI
Description: SelectAI is a model-agnostic software framework that wraps around existing machine learning and deep learning models to determine when predictions should be accepted or abstained from based on estimated reliability. By selectively deferring uncertain predictions, the software improves the accuracy of retained predictions.
Publication: In preparation.

Software from the Reed Group

Scott Reed

For more information about Professor Reed’s software contact him at SCOTT.REED@UCDENVER.EDU 

Name: ChemIllusion
Description: A web-based chemistry platform designed for students, educators, and researchers. Its main purpose is to help users create, edit, visualize, and teach chemistry using accurate molecular drawings and AI-assisted tools. Contains: Chemical structure drawing – Draw molecules, reactions, stereochemistry, resonance structures, and mechanisms in a browser-based editor; AI-assisted chemistry – Generate and edit molecular structures, reaction schemes, and chemistry illustrations while using chemistry-specific validation to reduce incorrect structures; Educational tools – Interactive lessons teach bond-line notation, rings, stereochemistry, lone pairs, formal charges, and reaction drawing. Instructors can build and share assignments with students; Course material creation – Instructors can generate textbooks, lecture slides, animations, tutorials, and practice exercises from a syllabus or concept map; Research graphics – Produce publication-quality figures, graphical abstracts, reaction diagrams, 3D molecular renderings, Newman projections, reaction coordinate diagrams, and other chemistry illustrations; Collaboration Tools– Share molecular canvases via links or QR codes for teaching or collaborative research; and other features.
Publication: https://chemillusion.com/

Name: OpenMolClaw
Description: An open, local-first chemistry agent harness for Ketcher, RDKit, and model-driven skills from the team behind ChemIllusion; runs the chemistry workspace on your own machine and lets you choose the model endpoint explicitly. Draw or paste a molecule in Ketcher, validate and canonicalize it with RDKit, render an SVG, and drive chemistry tools through a router-first agent loop
Publication: https://github.com/scottmreed/openmolclaw

Name: LLM SMILES/SMARTS Arena
Description: A benchmark suite for evaluating large language models on chemical string reasoning with SMILES, SMARTS, and SMIRKS; this benchmark is designed to stress tokenization-sensitive structure reasoning, not just broad chemistry recall.
Publication: https://github.com/scottmreed/llm-smarts-arena

Name: Moodle-local_Chemillusion
Description: ChemIllusion Study Tools for Moodle (local_chemillusion); A privacy-aware, open-source Moodle chemistry study plugin: molecule lookup, RDKit.js-powered browser-side structure rendering, functional-group highlighting, student flashcards, accessible summaries, and optional ChemIllusion account linking for richer AI, image, video, and teacher workflows.
Publication: https://github.com/scottmreed/moodle-local_chemillusion

Name: rdkit-agent
Description: Agent-first cheminformatics CLI powered by RDKit WASM. Validates, converts, and analyzes chemical notation (SMILES, SMIRKS, InChI) with structured JSON output. Works as a CLI, Node.js library, and MCP server.
Publication: https://github.com/scottmreed/rdkit-agent

Name: ChemCP
Description: An MCP App that renders interactive 2D molecular structure diagrams from SMILES notation using RDKit.js. Ask your AI assistant to show you any molecule, e.g. "Show me the structure of ibuprofen" and ChemCP displays the structure with computed properties — right inside the chat. You get: 2D structure diagrams rendered from any valid SMILES string; Molecular properties including molecular weight, LogP, H-bond donors/acceptors, TPSA, rotatable bonds, rings, and more; Interactive UI to click on example molecules or enter your own SMILES.
Publication: https://github.com/scottmreed/ChemCP

Software from the Wang Group

Haobin Wang

For more information about Professor Wang’s software, contact him at HAOBIN.WANG@UCDENVER.EDU

Name: SCHPACK
Description: SCH stands for 'self-consistent hybrid', which is a mixed quantum-classical strategy. The core part of the code is multilayer multiconfiguration time-dependent Hartree (ML-MCTDH) theory, nowadays called tree tensor network method. It can calculate various time correlation functions, linear and nonlinear spectroscopy, and thermal rate constant based on reactive flux correlation function formalism, for condensed phase models.
Publication: This is unpublished software.