Understanding Configurational Changes in Drug Molecules

A drug molecule may exist in multiple isomeric forms within its crystalline structure (called drug polymorphism), some of which can even be harmful for human consumption. A well-known example is the case of Norvir capsules (Abbott), a key HIV treatment containing ritonavir, which in 1998 underwent an unexpected transformation to a more stable crystal form. This change significantly reduced the drug’s solubility and bioavailability, ultimately leading to a temporary market withdrawal and disruption of patient treatment. The issue was later resolved through reformulation, underscoring the critical importance of monitoring and controlling the physical stability of pharmaceutical solids. In this study, we aim to investigate multiple isomeric forms of selected drug molecules and assess the likelihood of interconversion between them using computational methods.

Name of research group, project, or lab
PI: Alexandra Zagalskaya, Lab: Computational Chemistry & Materials Lab (ccML), Department of Chemical and Biomolecular Engineering
Why participate in this opportunity?

This project integrates advanced computational simulation techniques with the development of predictive molecular models, offering a unique opportunity to contribute to impactful, real-world scientific challenges. Participation will provide hands-on experience in state-of-the-art computational research while fostering critical problem-solving skills. Moreover, involvement in this project can serve as a strong foundation for future pursuits in advanced research, graduate studies, or careers within the biomedical and pharmaceutical industries.

Representative publication or further information
Logistics Information:
Subject Category
Biochemistry & Molecular Biology
Biomedical Engineering
Chemical Engineering
Chemistry
Physics
Science (Interdepartmental)
Student ranks applicable
Freshman
Sophomore
Junior
Senior
Student qualifications

An academic background in Chemical Engineering, Chemistry, Biochemistry, Materials Science, Physics, Computer Engineering, or a closely related field is required. Enthusiasm for developing new skills in computational modeling is essential.

Time commitment
8-10 h/wk
Position Types and Compensation
Research - Independent Study or Research Assistant credit
Research - Volunteer
Number of openings
2
Techniques learned

This project is fully computational. Students can expect to gain experience with the following methods: 1) density functional theory (DFT), 2) ab-initio molecular dynamics (AIMD), 3) enhanced sampling techniques (metadynamics, slow-growth approach). Simulations will be conducted on high-performance computing (HPC) resources using the VASP software. Additionally, students will learn data analysis and molecular visualization techniques, using tools like VMD and OVITO to interpret simulation results.

Project start
Spring 2026, Summer 2026
Contact Information:
Mentors
shubhamchatt@umass.edu
azagalskaya@umass.edu
Principal Investigator
Name of project director or principal investigator
Alexandra Zagalskaya
Email address of project director or principal investigator
azagalskaya@umass.edu
2 sp. | 16 appl.
Hours
8-10 h/wk
Project categories
Science (Interdepartmental) (+5)
Biochemistry & Molecular BiologyBiomedical EngineeringChemical EngineeringChemistryPhysicsScience (Interdepartmental)