Call For Papers: Modeling the Impact of Protein Mutations on Chemical Reactions for Biochemistry, Protein Engineering, and Drug Discovery

Protein mutations profoundly influence biochemical function, enzyme specificity, molecular mechanisms, and drug response, yet theoretical and computational tools still struggle to accurately quantify these effects. Challenges such as epistasis, sparse experimental mutagenesis data, and limited treatment of insertions, deletions, and excited‑state processes highlight gaps in our ability to reliably assess mutation impacts. Closing these gaps is essential for progressing biochemistry, protein engineering, and drug discovery.

The Journal of Chemical Theory and Computation (JCTC) is launching a Special Issue that assembles state‑of‑the‑art computational approaches for understanding and predicting how mutations reshape proteins’ chemical reactivity and function. This collection will highlight theoretical innovations, mechanistic insights, benchmark resources, and predictive methodologies that advance a unified framework for studying mutation effects across molecular life science disciplines.

Topics include, but are not limited to:

• Quantum chemistry, molecular mechanics, and QM/MM methods for analyzing mutation‑dependent changes in energetics and reaction mechanisms.
• Physics‑informed machine learning and data‑driven simulations for predicting effects on enzyme stability, function, and resistance.
• Integration of physics‑based modeling with sequence/structure‑based bioinformatics for high‑throughput mutation screening.
• Protocols and software tools for evaluating mutation‑induced changes in substrate binding, transition states, or reaction rates.
• Case studies of predictive modeling applied to natural evolution, clinical drug resistance, and directed evolution campaigns.

This Special Issue welcomes both original research and perspectives that identify current challenges and emerging opportunities at the intersection of computation, theory, and enzymology. Read the editorial for more information.

Organizing Editors

Zhongyue (John) Yang, Guest Editor, JCTC
Vanderbilt University, United States

Sijia S. Dong, Guest Editor, JCTC
Northeastern University, United States

Submission Information

We welcome submissions for this Special Issue through June 1, 2026. For more information on submission requirements, please visit the journal’s Author Guidelines page.

Accepted manuscripts for consideration in this Special Issue will include research articles and perspectives. Papers accepted for publication for this Special Issue will be available ASAP (as soon as publishable) online. After all submissions have been published, they will then be compiled online on a dedicated landing page to form the Special Issue. Manuscripts submitted for consideration will undergo the full rigorous peer review process expected from ACS journals.

Open Access: There are diverse open access options for publications in American Chemical Society journals. Please visit our Open Science Resource Center for more information.

How to Submit

• Log in to the ACS Publishing Center.
• Select the "Journals" tab.
• Choose Journal of Chemical Theory and Computation.
• Click "Submit."
• Select your manuscript type, and, under "Special Issue Selection," choose “Modeling the Impact of Protein Mutations on Chemical Reactions for Biochemistry, Protein Engineering, and Drug Discovery."

If you have any general questions regarding submission to this Special Issue, please contact managing.editor@jctc.acs.org.