Research Advisor, Computational Chemistry

At Lilly, we unite caring with discovery to make life better for people around the world. We are a global healthcare leader headquartered in Indianapolis, Indiana. Our employees around the world work to discover and bring life-changing medicines to those who need them, improve the understanding and management of disease, and give back to our communities through philanthropy and volunteerism. We give our best effort to our work, and we put people first. Weu2019re looking for people who are determined to make life better for people around the world. At Lilly, we unite caring with discovery to make life better for people around the world. We are a global healthcare leader headquartered in Indianapolis, Indiana. Our employees work to discover and bring life-changing medicines to those who need them, improve the understanding and management of disease, and give back to our communities through philanthropy and volunteerism. We give our best effort to our work, and we put people first. Weu2019re looking for people who are determined to make life better for people around the world. We are seeking a highly motivated computational chemist to join our team and apply physicsu2011based modeling and cheminformatics to the design of chemically modified oligonucleotide therapeutics. The Lilly Genetic Medicine (LGM) organization is an innovationu2011focused group dedicated to identifying, developing, and applying cuttingu2011edge technologies to maximize patient benefit. Our Data Science and AI/ML team partners closely with medicinal chemists, biologists, and data scientists across disciplines, playing a central role in molecular design, study design, and datau2011driven decisionu2011making to accelerate RNA drug discovery. Oligonucleotide therapeuticsu2014including siRNAs, ASOs, and spliceu2011switching oligonucleotidesu2014occupy a unique chemical space between small molecules and biologics. Each position in a therapeutic oligonucleotide can carry distinct sugar, backbone, and base modifications, creating a vast combinatorial design space that is poorly served by conventional computational chemistry tools. This role will bridge molecular simulation, cheminformatics, and machine learning to generate actionable insights that guide the optimization of chemically modified oligonucleotides across Lillyu2019s RNA therapeutics portfolio. Responsibilities: In this role, you will apply and develop computational chemistry methods to understand how chemical modifications influence the structure, stability, target engagement, and pharmacological properties of therapeutic oligonucleotides. You will work closely with medicinal chemists, biologists, and data scientists to translate atomicu2011level insights into design recommendations that advance portfolio programs and platform capabilities. Key responsibilities include: + Perform molecular dynamics simulations of chemically modified oligonucleotide duplexes and singleu2011stranded species to characterize the structural and thermodynamic consequences of sugar, backbone, and base modifications + Apply free energy methods (FEP, thermodynamic integration, MM/PBSA, MM/GBSA) to predict modificationu2011dependent binding affinities, duplex stability, and proteinu2013oligonucleotide interactions + Develop and validate force field parameters for novel nucleotide analogs using quantum mechanical calculations, enabling rapid computational evaluation of new chemistries emerging from the medicinal chemistry team + Build and apply cheminformatics descriptors and QSAR/QSPR models adapted for chemically modified oligonucleotides, moving beyond sequenceu2011only representations to capture the full chemical diversity of the modification space + Collaborate with medicinal chemists and biologists to integrate computational predictions with experimental SAR data, contributing to the identification of optimal modification patterns for onu2011target potency, selectivity, metabolic stability, and safety + Contribute to reusable computational workflows, data assets, and modeling platforms that support crossu2011program learning and integration with the teamu2019s unified machine learning models + Present findings to crossu2011functional teams and contribute to scientific strategy discussions, publications, and patent applications Basic Requirements: + PhD in computational chemistry, physical chemistry, chemical physics, biophysics, or a closely related field Additional Skills/Preferences: + Demonstrated expertise in molecular dynamics simulation of nucleic acids or chemically modified biopolymers + Experience with free energy calculation methods applied to biomolecular systems + Proficiency in cheminformatics toolkits (RDKit, OpenEye, or equivalent) and/or commercial CADD platforms (Schru00f6dinger, MOE) + Strong programming skills in Python, with experience in scientific computing libraries + Familiarity with machine learning and AI methods applied to molecular sciences, including experience with predictive modeling for molecular properties, chemical optimization, or structureu2013activity relationships + Excellent written and oral communication skills with ability to present complex computational results to diverse scientific audiences including medicinal chemists and biologists + Experience with highu2011performance computing and/or cloudu2011based simulation environments + Demonstrated ability to work collaboratively in crossu2011functional team environments + Experience with force field parameterization for nonu2011standard nucleotide analogs, including QMu2011derived charge fitting (RESP, AM1u2011BCC) and torsion parameter development + Familiarity with quantum chemical methods (DFT, ab initio) for electronic structure analysis of modified nucleotides and their impact on duplex stability and reactivity + Understanding of how chemical modifications influence oligonucleotide secondary structure, folding, and conformational dynamics, including modificationu2011dependent effects on duplex geometry and protein recognition + Experience with machine learning approaches for molecular property prediction, including graph neural networks, molecular language models, or transformeru2011based architectures applied to chemical or biopolymer data + Familiarity with molecular representations for modified oligonucleotides (HELM, extended SMILES, or similar macromolecular encoding schemes) + Knowledge of oligonucleotideu2011specific ADME properties, including nucleaseu2011mediated metabolism, plasma protein binding of phosphorothioate backbones, and endosomal escape + Track record of peeru2011reviewed publications demonstrating expertise in computational chemistry applied to nucleic acids or modified biopolymers + Deep understanding of nucleic acid structure and chemistry, including familiarity with common therapeutic modifications (2u2019u2011OMe, 2u2019u2011F, 2u2019u2011MOE, LNA/cET, phosphorothioate, GalNAc conjugates) + Experience designing computational workflows that integrate with automated experimental platforms and highu2011throughput screening + Proficiency in Rust or other systemsu2011level languages for performanceu2011critical scientific computing is a plus Lilly is dedicated to helping individuals with disabilities to actively engage in the workforce, ensuring equal opportunities when vying for positions. If you require accommodation to submit a resume for a position at Lilly, please complete the accommodation request form ( ) for further assistance. Please note this is for individuals to request an accommodation as part of the application process and any other correspondence will not receive a response. Lilly is proud to be an EEO Employer and does not discriminate on the basis of age, race, color, religion, gender identity, sex, gender expression, sexual orientation, genetic information, ancestry, national origin, protected veteran status, disability, or any other legally protected status. Our employee resource groups (ERGs) offer strong support networks for their members and are open to all employees. Our current groups include: Africa, Middle East, Central Asia Network, Black Employees at Lilly, Chinese Culture Network, Japanese International Leadership Network (JILN), Lilly India Network, Organization of Latinx at Lilly (OLA), PRIDE (LGBTQ+ Allies), Veterans Leadership Network (VLN), Womenu2019s Initiative for Leading at Lilly (WILL), enAble (for people with disabilities). Learn more about all of our groups. Actual compensation will depend on a candidateu2019s education, experience, skills, and geographic location. The anticipated wage for this position is $166,500 - $266,200 Full-time equivalent employees also will be eligible for a company bonus (depending, in part, on company and individual performance). In addition, Lilly offers a comprehensive benefit program to eligible employees, including eligibility to participate in a company-sponsored 401(k); pension; vacation benefits; eligibility for medical, dental, vision and prescription drug benefits; flexible benefits (e.g., healthcare and/or dependent day care flexible spending accounts); life insurance and death benefits; certain time off and leave of absence benefits; and well-being benefits (e.g., employee assistance program, fitness benefits, and employee clubs and activities).Lilly reserves the right to amend, modify, or terminate its compensation and benefit programs in its sole discretion and Lillyu2019s compensation practices and guidelines will apply regarding the details of any promotion or transfer of Lilly employees. #WeAreLilly

Created: 2026-03-07