Sandun Fernando

Areas of Expertise

• Computationally guided therapeutic and biocide design for undruggable and resistance-prone targets (antiviral, antimicrobial, anticancer)
• Biosensing and diagnostic ligand development (high-affinity, selective recognition)
• Catalysis

Professional Summary

Our laboratory is dedicated to understanding and harnessing biomolecular interactions to design molecules with precision, selectivity, and purpose. Biological systems function through intricate networks of intermolecular interactions, and decoding these processes at the molecular level enables the rational engineering of solutions critical to human health, agriculture, and sustainable energy. To achieve this, we integrate advanced molecular dynamics–guided computational design with rigorous experimental validation.

Our research centers on the molecular-level design and optimization of peptides, aptamers (oligonucleotides), and antibodies that precisely modulate enzyme activity, protein–protein interactions, and immune responses. These design principles are applied across several high-impact areas:

• Pathogen resistance and control, by targeting essential enzymes and surface proteins in bacterial, viral, and fungal pathogens.
• Biosensing and diagnostics, using high-affinity peptides and aptamers for rapid, selective, and miniaturizable molecular recognition platforms.
• Antibody optimization, by refining complementarity-determining regions (CDRs) and interfacial residues to enhance binding affinity, stability, and immune functionality.
• Catalysis and energy applications, through the engineering of enzyme-mimetic and redox-active systems for bioenergy and green chemistry.

At the core of our research is the Highly Optimized Peptide and Biopolymer Engineering (HOPE) algorithm, an advanced computational platform developed in our laboratory, for the rational design of highly specific, high-affinity peptides, aptamers, and antibodies. HOPE leverages molecular dynamics simulations to model ligand–receptor interactions within fully flexible, solvent-realistic environments. By systematically identifying and quantifying the most energetically favorable residue–residue interactions from large-scale simulations, HOPE directly informs the design of optimized molecular ligands.

HOPE routinely generates compact peptides (<2 kDa) with exceptionally strong binding affinities, exhibiting MM-GBSA Gibbs free energies typically below –80 kcal/mol and frequently exceeding –100 kcal/mol – hallmarks of highly stable and specific ligand-receptor interactions.

A defining strength of the HOPE platform is its ability to design ligands with extraordinary target specificity. Unlike traditional drug discovery approaches that depend on well-defined binding pockets, HOPE enables targeting of broad, shallow, or conformationally dynamic protein surfaces that were previously considered “undruggable.” This capability positions HOPE to address urgent and emerging challenges, including antimicrobial resistance, viral evolution, and resistance to therapeutics, while opening new frontiers in precision molecular engineering.

Selected Publications

• Mallawarachchi, S., Irigoyen, S., Mandadi, K., Borneman, J., & Fernando, S. (2026). Design of Highly Specific Antimicrobial Peptides Targeting the BamA Protein of Candidatus Liberibacter Asiaticus. ACS Omega. https://doi.org/10.1021/acsomega.5c11153
• Mulgaonkar, N., Wang, H., Mallawarachchi, S., Růžek, D., Martina, B., & Fernando, S. (2023). In silico and in vitro evaluation of imatinib as an inhibitor for SARS-CoV-2. Journal of Biomolecular Structure and Dynamics, 41(7), 3052-3061. https://doi.org/10.1080/07391102.2022.2045221
• Smith, B. L., Fernando, S., & King, M. D. (2024). Escherichia coli resistance mechanism AcrAB-TolC efflux pump interactions with commonly used antibiotics: a molecular dynamics study. Scientific Reports, 14(1), 2742. https://doi.org/10.1038/s41598-024-52536-z
• Wang, H., Mulgaonkar, N., Pérez, L. M., & Fernando, S. (2022). ELIXIR-A: An Interactive Visualization Tool for Multi-Target Pharmacophore Refinement. ACS Omega, 7(15), 12707-12715. https://doi.org/10.1021/acsomega.1c07144
• Samarasinghe, N., Longtin, N., & Fernando, S. (2022). Performance of Methylococcus capsulatus based microbial and enzymatic proton exchange membrane fuel cells. Renewable Energy, 195, 17-27. https://doi.org/https://doi.org/10.1016/j.renene.2022.06.023
• Mahadevan, A., Verkhoturov, S., Vaddiraju, S., Pietz, M., Di Carlo, P., & Fernando, S. (2022). Direct wiring of redox cofactors onto gold electrodes via inorganic iron-sulfur clusters enhances charge transport. Biosensors and Bioelectronics: X, 12, 100279. https://doi.org/https://doi.org/10.1016/j.biosx.2022.100279
• Zhang, J., Gelain, J., Schnabel, G., Mallawarachchi, S., Wang, H., Mulgaonkar, N., Karthikeyan, R., & Fernando, S. (2023). Identification of Fungicide Combinations for Overcoming Plasmopara viticola and Botrytis cinerea Fungicide Resistance. Microorganisms, 11(12), 2966. https://www.mdpi.com/2076-2607/11/12/2966

All Publications

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